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Resting State Functional Connectivity is Associated With Treatment Response in Major Depression: A Real World Study
- Y. Harrington, M. Paolini, V. Bettonagli, F. Colombo, S. Poletti, R. Zanardi, F. Benedetti
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S606-S607
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Introduction
Major depressive disorder (MDD) is largely considered the most prevalent psychiatric disorder worldwide. Despite its domineering presence, effective treatment for many individuals remains elusive. Investigation into relevant biological markers, specifically neuroimaging correlates, of MDD and treatment response have gained traction in recent years; however, findings are still inconsistent.
ObjectivesIn this study, we aimed to investigate the resting state functional connectivity patterns associated with treatment response in MDD inpatients in a real world setting.
MethodsForty-three inpatients suffering from a major depressive episode were recruited from the psychiatric ward at IRCCS San Raffaele Hospital in Milan, Italy. Symptom severity was assessed via the 21-item Hamilton Depression Rating Scale (HDRS). The percentage of decrease in HDRS scores from admission to discharge was then calculated with the formula [(HDRS admission – HDRS discharge) * 100] / HDRS admission. All patients underwent a 3T MRI scan within one week of admission to acquire resting-state fMRI images, which included 200 sequential T2*-weighted volumes. Images were preprocessed using the CONN toolbox, running within Statistical Parametric Mapping (SPM 12). Preprocessing was performed according to a standard pipeline. A voxel-wise metric, intrinsic connectivity contrast (ICC), was implemented to explore the global resting state functional connectivity (rs-FC) patterns associated with treatment response. ICC-derived maps were then entered in the second-level analyses to examine the effect of the percentage of HDRS decrease, including age, sex, admission HDRS score, duration of hospitalization, and antidepressant dose equivalents as nuisance covariates.
ResultsWe found that the percentage of HDRS decrease after treatment predicted rs-FC. ICC analysis identified 2 clusters where changes in HDRS scores were significantly associated with rs-FC, with increased connectivity in the supramarginal gyrus (pFDR = 0.002) and decreased connectivity in the amygdala and parahippocampal gyrus (pFDR = 0.047).
ConclusionsOur results suggest that altered connectivity of the supramarginal gyrus, amygdala and parahippocampal gyrus is related to antidepressant treatment response. Given that these brain areas are implicated in emotional processing and mood, it is conceivable that a better integrity of brain connectivity may facilitate treatment response in major depression.
Disclosure of InterestNone Declared
Inflammatory signature of post-COVID-19 depression
- M. Palladini, M. G. Mazza, V. Aggio, S. Spadini, F. Calesella, S. Poletti, P. Rovere-Querini, F. Benedetti
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S123-S124
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Introduction
Persisting and disabling depressive symptomatology represent a prominent feature of the post-acute COVID-19 syndrome. Sars-CoV-2-induced immune system dysregulation mainly result in a cytokine storm. Once in the brain, inflammatory mediators negatively affect neurotransmission, microglia activation, and oxidative stress, possibly disrupting critical brain neurocircuits which underpin depressive symptoms. So far, only inflammatory markers based on leukocyte counts have been linked to depressive outcome in COVID survivors. However, an accurate immune profile of post-COVID depression has yet to be elucidated.
ObjectivesIdentify inflammatory mediators that predict post-COVID depression among a panel of cytokines, chemokines, and growth factors, with a machine learning routine.
Methods88 COVID age- and sex-matched survivors’ (age 52.01 ± 9.32) were screened for depressive symptomatology one month after the virus clearance through the Beck Depression Inventory (BDI-13), with 12.5% of the individuals scoring in the clinical range (BDI-13 ≥ 9). Immune assay was performed through Luminex system on blood sampling obtained in the same context. We entered 42 analytes into an elastic net penalized regression model predicting presence of clinical depression, applied within a 5-fold nested cross-validation machine learning routine running in MATLAB. Significance of predictors was evaluated according to variable inclusion probability (VIP), as returned by 5000 bootstraps. Socio-demographics, previous psychiatric history, hospitalization, time after discharge were used as covariates.
ResultsThe model reached a balance accuracy of 73% and AUC of 77%, correctly identifying 73% of people suffering from clinically relevant depressive symptoms (Figure1). Depressive symptomatology was predicted by high levels of CCL17, ICAM-1, MIF, whereas CXCL13, CXCL12, CXCL10, CXCL5, CXCL2, CCL23, CCL15, CCL8, GM-CSF showed a protective effect (Figure2).
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ConclusionsThis is the first study highlighting a putative inflammatory signature of post-COVID depression. Consistently to the immune profile of Major Depressive disorder, upregulation of innate immunity mediators seems to foster depressive symptoms in the aftermath of COVID. Interestingly, recruiters of B and T cells promoting a physiological adaptive response to viral infection also mitigate its psychiatric sequelae. Understanding the biological basis of post-COVID depression could pave the way for personalized treatments capable of reducing its add-on burden.
Disclosure of InterestNone Declared
Time Moderates the interplay between 5-HTTLPR and stress on depression risk: gene x environment interaction as dynamic process
- C. Delli Colli, S. Poggini, M. Borgi, B. Vai, F. Cirulli, B. W. J. H. Penninx, F. Benedetti, F. Chiarotti, I. Branchi
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S221
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Introduction
The role of the interaction between the serotonin-transporter-linked promoter region (5HTTLPR) and stressful condition in determining the vulnerability to depression has been widely investigated. Nevertheless, empirical research provides contrasting findings. Recently, the differential susceptibility to environment model proposed a conceptual shift respect to the classical interpretation of 5-HTTLPR: viewing the short (s) and the long (l) allele not as associated to different traits of vulnerability (respectively vulnerable or not), but determining different plasticity levels (respectively, more and less plasticity) and, thus, different susceptibilities to the environment (respectively, high and low susceptibility).
ObjectivesAs 5-HTTLPR is involved in plasticity, the main goal of the present study is to demonstrate that the interaction between the polymorphism and stress emerges when assessing its effects according to temporal factors in a dynamic process perspective.
MethodsWe explored our hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. We applied the DerSimonian and Laird random-effects model to estimate crude odds ratios for risk of depression according to 5HTTLPR and we assessed heterogeneity using the I² and Cochran’s Q statistic. We stratified the staties according to (i) stress duration (i.e., chronic vs. acute stress) and (ii) time elapsed between the end of the stressful condition and the assessment of depression (i.e., within one year vs. more than one year).
ResultsWhen stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress (OR 1.43, 95%IC 1.16-1.77, I²= 52%, Q=25.25; Figure 1), with a significant subgroup difference (p=0.004). The stratification according to time interval revealed a significant interaction only for intervals within one year (OR 1.23, 95%IC 1.03-1-46, I²= 67%, Q=39.35), though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within one year (OR 1.53, 95%IC 1.17-2.02, I²= 45%, Q=10.94; Figure 2) and a significant subgroup difference was found (p=0.01).
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ConclusionsOur results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time-points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, resulting in a three-way interaction: gene x environment x time.
Disclosure of InterestNone Declared
Brain correlates of perceived cognitive impairment after covid-19 infection: a multimodal MRI study.
- V. Bettonagli, M. Paolini, M. Palladini, M. G. Mazza, P. Rovere Guerini, S. Poletti, F. Benedetti
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S120
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Introduction
Many different long-term neuropsychiatric sequelae of the novel Coronavirus have been described after the pandemic outbreak. One of the most common symptoms in the months following infection is related to “brain fog”. This condition includes several signs of cognitive impairment like mental slowness, deficits in attention, executive functions, processing, memory, learning, and/or psychomotor coordination, which can be perceived on a subjective level and further confirmed by objective data. Since this kind of mental status has been documented in previous viral infections, and the SARS-COV-2 has been characterized by a worldwide diffusion, investigation into this condition in post-covid individuals is warranted. Currently, several hypotheses on its pathophysiology have been put forward, mostly hypothesizing a direct effect of the virus on the central nervous system or indirect consequences of the inflammatory response.
ObjectivesThe aim of our research is to analyze brain correlates of subjective cognitive complaints in Covid-19 survivors using multimodal brain imaging.
MethodsWe performed a voxel-based morphometry (VBM) and a resting state functional connectivity analysis on 60 post-COVID-19 individuals recruited from the San Raffaele Hospital in Milan, that underwent a 3 tesla MRI scan. We assessed the perceived cognitive impairment both after the infection and at the time of the MRI scan through the PROMIS Cognitive Abilities scale. The difference of the two scores (delta PROMIS) was calculated as a measure of cognitive improvement over time.
ResultsWe found the perceived amelioration of cognitive abilities (delta PROMIS) to be positively associated to grey matter volumes in the bilateral caudate, putamen and pallidum (pFWE: ˂0.001). Moreover, in the resting state fMRI analysis, subjective cognitive status at MRI was found to be associated with functional connectivity between the right putamen and pallidum, and two clusters belonging to the attentional (pFWE: ˂0.001) and salience (pFWE: 0.02) networks.
ConclusionsThis is one of the first studies investigating brain correlates of subjective cognitive impairment after COVID-19 infection; our main finding is the convergence of structural and functional results on brain areas located within the basal ganglia, implying their possible role in the pathophysiology of the condition. Moreover, this research could be interpreted as the first step toward understanding a very complex condition, with potential implications for the development of treatment and neurorehabilitative strategies.
Disclosure of InterestNone Declared
Choroid plexus volume as a proxy of neuroinflammation in depression
- B. Bravi, E. Melloni, L. Servidio, E. Agnoletto, M. Paolini, S. Poletti, C. Lorenzi, C. Colombo, F. Benedetti
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S244-S245
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Introduction
Choroid plexus (CP) is a physiological barrier, producing cerebrospinal fluid (CSF), neurotrophic, and inflammatory factors. It’s also involved in the neuro-immune axis, facilitating the interplay between central and peripheral inflammation, allowing trafficking of immune cells. Coherently, CP enlargement has been found in psychiatric diseases characterized by inflammatory signature. Although CP volume correlates with central microglia activation in major depressive disorder (MDD), it’s never been directly associated with peripheral markers in mood disorders.
ObjectivesExamine CP volume in mood disorders and healthy controls (HC) in relation to clinical features and peripheral inflammatory markers.
MethodsCP volume was extracted with FreeSurfer in 72 HC and 152 age- and sex-matched depressed patients: 79 BD and 73 MDD. Plasma analytes in patients were collected through immunoassay technology (Bioplex). We tested for the effect of age by group on CP volume. Then we focused on the interaction between illness duration and diagnosis in predicting CP volume. After testing the effect of specific analytes by diagnosis, we calculated moderated moderation models (SPSS, PROCESS) setting each analyte as independent variable, CP volume as predicted variable and illness duration and diagnosis as moderators. We get the effects’ significance with the likelihood ratio statistic, always controlling for age, sex, and intracranial volume.
ResultsPatients were comparable in illness duration and severity. CP volume is differentially distributed through groups (right: p=0.04; left: p<0.01), with higher volumes in the clinical groups. Age by group significantly predict right CP volume (p=0.01). Also, duration of illness differently predicts right CP volume in MDD and BD (p=0.03) (Figure1). Then, given the significant interaction effect of IL13 (p=0.02) and IL1ra (p=0.01) in predicting right CP, we run the moderated moderation model. Longer illness duration has an effect in strengthening the opposite predicting value of IL1ra (ΔR2=0.03, p<0.01) on right CP volume in MDD and BD (Figure2).
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ConclusionsOur findings propose CP as a proxy of inflammation in depression, being significantly predicted by peripheral immune markers in MDD and BD. In particular, the signature of inflammation in depression, could represent the neurotoxic load of the disease over the illness, with a worse effect in BD, with possible disruption of brain barriers permeability and an opposite effect of tightening and central segregation in MDD. Further analyses are needed to better elucidate this neurobiological mechanisms across mood disorders.
Disclosure of InterestNone Declared
The different effect of adverse childhood experiences on Theory of Mind brain networks in schizophrenia and healthy controls
- A. Pelucchi, F. Calesella, M. Bechi, R. Cavallaro, S. Poletti, B. Vai, F. Benedetti
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S373-S374
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Introduction
Deficit in Theory of Mind (ToM) is a core feature of schizophrenia (SZ), while adverse childhood experiences (ACEs) can contribute to worsen ToM abilities through their effect on brain functioning, structure and connectivity.
ObjectivesHere, we investigated the effects of ACEs on brain functional connectivity (FC) during an affective and cognitive ToM task (AToM, CToM) in healthy control (HC) and SZ, and whether FC can predict the performance at the ToM task and patients’ symptoms severity.
MethodsThe sample included 26 HC and 33 SZ. In an fMRI session, participants performed a ToM task targeting affective and cognitive domains. Whole-brain FC patterns of local correlation (LC) and multivariate pattern analysis (MVPA) were extracted. The significant MVPA clusters were used as seeds in further seed-based connectivity analyses. Second-level analyses were modelled to investigate the interaction between ACEs, the diagnosis, and the task, corrected for age, sex, and equivalent doses of chlorpromazine (p<0.05 FWE). FC values significantly affected by ACEs (Risky Family Questionnaire) were entered in a cross-validated LASSO regression predicting symptoms severity (Positive and Negative Syndrome Scale, PANSS) and task performance measures (accuracy and response time).
ResultsIn AToM, LC showed significant different effects of ACE between HC and SZ in frontal pole, caudate and cerebellum. MVPA showed significant widespread interaction in cortico-limbic regions, including prefrontal cortex, precuneus, insula, parahippocampus, cingulate cortex, temporal pole, thalamus, and cerebellum in AToM and CToM. SBC analyses found significant target regions in the frontal pole, cerebellum, pre and postcentral gyrus, precuneus, lateral occipital cortex, angular gyrus, and paracingulate gyrus. LASSO regression predicted PANSS score (R2=0.49) and AToM response latency time (R2=0.37).
ConclusionsOur findings highlighted a widespread different effect of ACEs on brain FC in ToM networks in HC and SZ. Notably, the FC in these regions is predictive of behavioral ToM performance and clinical outcomes.
Disclosure of InterestNone Declared
Effect of Neutrophil to Lymphocyte ratio on antidepressant treatment response: moderating effect of sex and mediating effect of Hippocampal volumes.
- M. Paolini, Y. Harrington, J. Ernst, R. Zanardi, S. Poletti, F. Benedetti
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S246
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Introduction
In recent years much focus has been put on the role of immune/inflammatory alterations in affecting Major Depression (MDD) development and antidepressant efficacy. Neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker shown to be elevated in depressed patients, with large population studies reporting this effect only in women. However, its relation to treatment response is much less clear. Reduced hippocampal volumes (HV) are among the few consistent brain structural predictors of poor treatment response, and they have been shown to be influenced by inflammatory status.
ObjectivesTo investigate the effect of NLR on treatment response in MDD patients, testing a possible moderating role of sex. To investigate the effect of NLR on HV and test a possible mediating role of the latter in the relation between NLR and treatment response.
MethodsOur study was performed on a sample of 120 MDD inpatients suffering from a non psychotic depressive episode (F=78; M=42). Depression severity was assessed via the Hamilton Depression Rating Scale (HDRS), both at admission and discharge; as a measure of treatment response, delta HDRS was calculated subtracting the two scores. NLR was calculated for each subject. Patients underwent 3T MRI acquisition and bilateral HV were estimated.
ResultsWe found a significant moderating effect of sex on the relationship between NLR and Delta HDRS (p < 0.001): a negative relation was found in women (p < 0.001) and a positive one in men (p = 0.042). NLR was found to negatively affect left HV in the whole sample (p = 0.027) and in women (p = 0.038). A positive effect on Delta HDRS was found for both left (p = 0.038) and right (p = 0.027) HV. Finally, we found a significant indirect effect of NLR values on Delta HDRS through left HV in women (95% BCa CI [- 0.948, -0.017]); the direct effect of NLR on Delta HDRS also remained significant (p = 0.002).
ConclusionsSex was found to moderate the relation between NLR and treatment response. The detrimental effect in women is in line with previous reports linking inflammation to hampered antidepressant effect; the positive one in men is more surprising: however, the only studies to date on the effect of NLR on antidepressant efficacy report a positive effect in patients with psychotic depression. In women we found NLR to affect treatment response partially through its effect on left HV, providing a possible, albeit incomplete, mechanistic explanation of the effect of inflammatory status on antidepressant efficacy.
Disclosure of InterestNone Declared
Global signal topography of the depressive syndrome in bipolar disorder
- G. Gulino, A. Scalabrini, M. Paolini, M. Palladini, F. Benedetti
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S549
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Introduction
Previous findings show that the depressive state is characterized by a peculiar suppression of the resting state functional connectivity (rsFC) anti-correlation between resting-state networks (e.g., Default Mode Network) and task-positive networks (e.g., Sensory-Motor Network) in favor of an abnormal positive rsFC pattern. This suggests a large-scale functional disbalance in adaptively switching the attentional focus from an internal-oriented cognitive modality to an external-oriented processing modality. Yet, according to further evidence, such a functional inversion is primarily driven by the global signal (GS) (i.e., by an abnormal large-scale topographical reconfiguration) in major depressive disorder (MDD). However, it is not clear if similar alterations may affect bipolar disorder (BD) in depressive phase.
ObjectivesInvestigation of the global topography of the depressive syndrome as a potential transnosographic endophenotype and evaluation of the GS on generating differences between groups.
MethodsWe compared large-scale rsFC patterns in a group of healthy controls (HC) (n=70) and a group of patients with BD (n=70) during a depressive episode. In order to investigate the impact of the GS, we further performed all analyses both with and without GS regression (GSR).
ResultsCompared to HC, patients with an ongoing major depressive episode exhibit specific resting-state changes that are only observed when analysis is performed without regressing GS. Patients were found to exhibit an (i) abnormally strong GS contribution within an extended cluster comprising regions known to be part of highly interconnected hubs (i.e., transmodal networks) and showing functional relations’ core along the cortical midline and a (ii) diminished influence of the GS in correspondence of frontoparietal and occipitotemporal regions. Notably, no traces of such changes -differentiating the global topography of patients from HC- held when applying GSR.
ConclusionsOur results (i) suggest that rsFC alterations detected stem from a global rather than a local source and (ii) corroborate the impact GS can exert on generating within and between-networks differences. Hence, we underline the necessity that future investigations on groups with expected altered topographical distribution include GS within data-analysis and a proper evaluation of its involvement. Nonetheless, our results are in line with previous evidence of altered global topography in MDD. Hence, we interpreted this finding as a benchmark of a whole-brain functional disbalance toward self-oriented cognition characterizing the transnosographic depressive syndrome.
Disclosure of InterestNone Declared
The exploration of interoception construct in COVID-19 survivors
- G. D’Orsi, M. Palladini, A. Scalabrini, M. G. Mazza, S. Poletti, P. Rovere-Querini, F. Benedetti
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S791-S792
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Introduction
The new coronavirus disease (COVID-19) has important physical and mental health implications at short and long term. Some inflammatory parameters are implicated in the maintenance of psychiatric symptoms, especially those of anxiety and depression. Additionally, growing literature attributes a role to interoception in several mental health conditions.
ObjectivesWe investigated the involvement of the interoception in COVID-19 survivors and its possible associations with psychopathological and inflammatory variables.
MethodsOur study included 57 people surviving COVID-19 at one month follow-up after recovery. Individual interoceptive accuracy (IA) measure was obtained through heart-beat perception task. A measure of accuracy in external time perception (TA) was also obtained asking people to mentally produce a duration of 10s. Each participant completed State-Trait Anxiety Inventory - STAI-Y; Zung Self-Rating Depression Scale - ZSDS; Beck Depression Inventory - BDI-II; Impact of Events Scale - IES-R and Multidimensional Assessment of Interoceptive Awareness - MAIA. Peripheral inflammation markers were obtained in a subsample of 40 people by a blood sampling conducted at the time of admission and discharge from hospital. Correlation, regression and GLM analyses were performed with SPSS. Mediation analysis were performed with Hayes’ Process tool.
ResultsTA is not associated with IA, symptomatological measures and bodily awareness. Trusting is the only aspect of body awareness associated with IA (p=.021). Noticing (p=.010), Not-distracting (p=.009), Not-worrying (p=.012) and Trusting (p=.001) predict anxiety psychopathology. Poor IA predict anxiety symptomatology (p=.004) and part of this effect is mediated by Trusting [Fig.1]. In the end, platelets count at the time of hospitalization negatively correlates with anxiety symptoms (p=.003).
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ConclusionsCOVID-19 hospitalization could be considered a psychophysical traumatic experience which involved mental and physical health and the connection and integration between them. It’s necessary to deepen the different facets of body awareness and IA in post-covid stages and to study how interoceptive dimensions change over time. Further research is needed to investigate the specific role of platelets in prominent anxiety psychopathology detected in COVID-19 survivors, wondering about their possible involvement in the dysfunctional interoception process too.
Disclosure of InterestNone Declared
Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants
- Sean R. McWhinney, Christoph Abé, Martin Alda, Francesco Benedetti, Erlend Bøen, Caterina del Mar Bonnin, Tiana Borgers, Katharina Brosch, Erick J. Canales-Rodríguez, Dara M. Cannon, Udo Dannlowski, Ana M. Diaz-Zuluaga, Lorielle M.F. Dietze, Torbjørn Elvsåshagen, Lisa T. Eyler, Janice M. Fullerton, Jose M. Goikolea, Janik Goltermann, Dominik Grotegerd, Bartholomeus C. M. Haarman, Tim Hahn, Fleur M. Howells, Martin Ingvar, Neda Jahanshad, Tilo T. J. Kircher, Axel Krug, Rayus T. Kuplicki, Mikael Landén, Hannah Lemke, Benny Liberg, Carlos Lopez-Jaramillo, Ulrik F. Malt, Fiona M. Martyn, Elena Mazza, Colm McDonald, Genevieve McPhilemy, Sandra Meier, Susanne Meinert, Tina Meller, Elisa M. T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadic, Nils Opel, Roel A. Ophoff, Bronwyn J. Overs, Julia-Katharina Pfarr, Julian A. Pineda-Zapata, Edith Pomarol-Clotet, Joaquim Raduà, Jonathan Repple, Maike Richter, Kai G. Ringwald, Gloria Roberts, Alex Ross, Raymond Salvador, Jonathan Savitz, Simon Schmitt, Peter R. Schofield, Kang Sim, Dan J. Stein, Frederike Stein, Henk S. Temmingh, Katharina Thiel, Sophia I. Thomopoulos, Neeltje E. M. van Haren, Cristian Vargas, Eduard Vieta, Annabel Vreeker, Lena Waltemate, Lakshmi N. Yatham, Christopher R. K. Ching, Ole A. Andreassen, Paul M. Thompson, Tomas Hajek, for the ENIGMA Bipolar Disorder Working Group
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 27 February 2023, pp. 6743-6753
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Background:
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Investigating the relationship between autistic traits and symptoms and Catatonia Spectrum
- L. Dell’Osso, G. Amatori, G. Massimetti, B. Nardi, D. Gravina, F. Benedetti, C. Bonelli, M. Luciano, I. Berardelli, N. Brondino, M. De Gregorio, G. Deste, M. Nola, A. Reitano, M. R. A. Muscatello, M. Pompili, P. Politi, A. Vita, C. Carmassi, M. Maj
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- Journal:
- European Psychiatry / Volume 65 / Issue 1 / 2022
- Published online by Cambridge University Press:
- 04 November 2022, e81
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Background
In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS).
MethodsA total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score.
ResultsA statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper–hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD.
ConclusionsOur study reports a strong correlation between autism spectrum and CS.
Radial density profile and stability of capillary discharge plasma waveguides of lengths up to 40 cm
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- M. Turner, A. J. Gonsalves, S. S. Bulanov, C. Benedetti, N. A. Bobrova, V. A. Gasilov, P. V. Sasorov, G. Korn, K. Nakamura, J. van Tilborg, C. G. Geddes, C. B. Schroeder, E. Esarey
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- Journal:
- High Power Laser Science and Engineering / Volume 9 / 2021
- Published online by Cambridge University Press:
- 26 April 2021, e17
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We measured the parameter reproducibility and radial electron density profile of capillary discharge waveguides with diameters of 650 $\mathrm{\mu} \mathrm{m}$ to 2 mm and lengths of 9 to 40 cm. To the best of the authors’ knowledge, 40 cm is the longest discharge capillary plasma waveguide to date. This length is important for $\ge$10 GeV electron energy gain in a single laser-driven plasma wakefield acceleration stage. Evaluation of waveguide parameter variations showed that their focusing strength was stable and reproducible to $<0.2$% and their average on-axis plasma electron density to $<1$%. These variations explain only a small fraction of laser-driven plasma wakefield acceleration electron bunch variations observed in experiments to date. Measurements of laser pulse centroid oscillations revealed that the radial channel profile rises faster than parabolic and is in excellent agreement with magnetohydrodynamic simulation results. We show that the effects of non-parabolic contributions on Gaussian pulse propagation were negligible when the pulse was approximately matched to the channel. However, they affected pulse propagation for a non-matched configuration in which the waveguide was used as a plasma telescope to change the focused laser pulse spot size.
Evaluation of a home-based 7-day infection control strategy for healthcare workers following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2): A cohort study
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- Carla Benea, Laura Rendon, Jesse Papenburg, Charles Frenette, Ahmed Imacoudene, Emily G. McDonald, Quoc D. Nguyen, Ewa Rajda, Estelle Tran, Motahareh Vameghestahbanati, Andrea Benedetti, Marcel A. Behr, Benjamin M. Smith
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 42 / Issue 10 / October 2021
- Published online by Cambridge University Press:
- 16 December 2020, pp. 1194-1197
- Print publication:
- October 2021
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Objective:
Evidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). In this study, we evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy.
Methods:HCWs advised by their infection control or occupational health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May and October 2020. The strategy consisted of symptom-triggered nasopharyngeal SARS-CoV-2 RNA testing from day 0 to day 7 after exposure and standardized home-based nasopharyngeal swab and saliva testing on day 7. The NPV of this strategy was calculated for (1) clinical coronavirus disease 2019 (COVID-19) diagnosis from day 8–14 after exposure, and for (2) asymptomatic SARS-CoV-2 detected by standardized nasopharyngeal swab and saliva specimens collected at days 9, 10, and 14 after exposure. Interim results are reported in the context of a second wave threatening this essential workforce.
Results:Among 30 HCWs enrolled, the mean age was 31 years (SD, ±9), and 24 (80%) were female. Moreover, 3 were diagnosed with COVID-19 by day 14 after exposure (secondary attack rate, 10.0%), and all cases were detected using the 7-day infection control strategy: the NPV for subsequent clinical COVID-19 or asymptomatic SARS-CoV-2 detection by day 14 was 100.0% (95% CI, 93.1%–100.0%).
Conclusions:Among HCWs with high-risk exposure to SARS-CoV-2, a home-based 7-day infection control strategy may have a high NPV for subsequent COVID-19 and asymptomatic SARS-CoV-2 detection. Ongoing data collection and data sharing are needed to improve the precision of the estimated NPV, and here we report interim results to inform infection control strategies in light of a second wave threatening this essential workforce.
PW01-29 - Mood Stabilizers and Atypical Antipsychotics in Long-term Treatment of Bipolar Disorder
- R. Paoli, M. Buoli, D. Primavera, M. Benedetti, C. Rovera, A.C. Altamura
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- Journal:
- European Psychiatry / Volume 25 / Issue S1 / 2010
- Published online by Cambridge University Press:
- 17 April 2020, 25-E1431
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Objectives
Bipolar Disorder treatment includes not only the remission of Major Depressive or Manic/Hypomanic Episodes, but also the prevention of recurrences. Purpose of this trial is to evaluate the effectiveness of Mood Stabilizers and Atypical Antipsychotics in preventing recurrences.
Methods67 patients with a diagnosis of Bipolar Disorder type 1 and 2 were followed retrospectively for a period of 48 months. Clinical and demographic information were collected by clinical charts and interviews with patients. A survival analysis was performed considering death events change of treatment, a Major Depressive or Hypomanic/Manic Episode or a hospitalization.
ResultsPatients treated with Lithium survived longer than patients treated with Valproate (Log Rank: χ2=3.86, p=0.05) which resulted to be superior in terms of recurrence prevention compared to Atypical Antipsychotics in monotherapy (Olanzapine, Quetiapine or Risperidone) (Log Rank: χ2=4.54, p=0.03). Lithium association with an Atypical Antipsychotic resulted more efficacious in terms of recurrence prevention compared to Lithium (Log Rank: χ2=7.01, p=0.008) or Atypical Antipsychotics in monotherapy (Log Rank: χ2=8.61, p=0.003).
ConclusionsThese preliminary data would indicate that Lithium association with an Atypical Antipsychotic would be more effective in preventing Major Depressive or Hypomanic/Manic recurrences in bipolar patients.
The nocebo effect: How stress modulates pain
- M. Sigaudo, S. Vighetti, F. Benedetti, L. Colloca
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- Journal:
- European Psychiatry / Volume 22 / Issue S1 / March 2007
- Published online by Cambridge University Press:
- 16 April 2020, p. S270
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Background and aims:
A close relationship between anxiety and pain has been demonstrated in different conditions. The nocebo effect, whereby a verbal stressor is capable of inducing hyperalgesia, has been shown to be a good model to study such a relationship. In particular, nocebo hyperalgesia has been found to be associated to the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and benzodiazepines can antagonize both nocebo hyperalgesia and HPA hyperactivity, thus suggesting that anxiety play a major role. Here we investigate how stressful stimuli can modulate pain.
Methods:As a stressor, we used a nocebo procedure whereby verbal suggestions of hyperalgesia were given to healthy volunteers before administration of either tactile or low-intensity painful stimuli. Pain perception was assessed by means of a Numerical Rating Scale (NRS), raging from 0= no pain to 10= unbearable pain. The nocebo procedure was carried out after a pre-conditioning session in which two different conditioned stimuli were associated to either pain or no pain.
Results:We found that the conditioned stimulus that was associated to pain was capable, when presented alone, of turning a tactile stimulus into pain.
Conclusions:These data suggest that a stressor, probably through anticipatory anxiety, can induce allodynic effects, whereby tactile stimuli become painful. These findings, along with previous data about placebo effects, indicate the powerful modulation of pain by placebos and nocebos.
A single nucleotide polymorphism in SLC1A1 gene is associated with age of onset of obsessive-compulsive disorder
- S. Dallaspezia, M. Mazza, C. Lorenzi, F. Benedetti, E. Smeraldi
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- Journal:
- European Psychiatry / Volume 29 / Issue 5 / June 2014
- Published online by Cambridge University Press:
- 15 April 2020, pp. 301-303
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Different genetic polymorphisms in the SLC1A1 have been shown to be associated with obsessive-compulsive disorder. Rs301430 is a T/C functional polymorphism affecting the gene expression and extrasynaptic glutamate concentration.We observed that Rs301430 influence age at onset in obsessive-compulsive disorder.
Effect of glutamate transporter EAAT2 gene variants and gray matter deficits on working memory in schizophrenia
- S. Poletti, D. Radaelli, M. Bosia, M. Buonocore, A. Pirovano, C. Lorenzi, R. Cavallaro, E. Smeraldi, F. Benedetti
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- Journal:
- European Psychiatry / Volume 29 / Issue 4 / May 2014
- Published online by Cambridge University Press:
- 15 April 2020, pp. 219-225
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Glutamate is the major excitatory neurotransmitter in the brain, with up to 40% of all synapses being glutamatergic. An altered glutamatergic transmission could play a critical role in working memory deficts observed in schizophrenia and could underline progressive changes such as grey matter loss throughout the brain. The aim of the study was to investigate if gray matter volume and working memory could be modulated by a genetic polymorphism related to glutamatergic function. Fifty schizophrenia patients underwent magnetic resonance and working memory testing outside of the scanner and were genotyped for rs4354668 EAAT2 polymorphism. Carriers of the G allele had lower gray matter volumes than T/T homozygote and worse working memory performance. Poor working memory performance was associated with gray matter reduction. Differences between the three genotypes are more relevant among patients showing poor performance at the 2-back task. Since glutamate abnormalities are known to be involved in excitotoxic processes, the decrease in cortical thickness observed in schizophrenia patients could be linked to an excess of extracellular glutamate. The differential effect of EAAT2 observed between good and poor performers suggests that the effect of EEAT2 on gray matter might reveal in the presence of a pathological process affecting gray matter.
Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis – ERRATUM
- Yin Wu, Brooke Levis, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Jill Boruff, Pim Cuijpers, Simon Gilbody, John P.A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Yeates Conwell, Janneke M. de Manvan Ginkel, Jesse R. Fann, Felix H. Fischer, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, Patricia A. Harrison, Martin Härter, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Yunxin Kwan, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Anthony McGuire, Sherina Mohd-Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Katrin Reuter, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Henk C. van Weert, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Andrea Benedetti, Brett D. Thombs
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- Journal:
- Psychological Medicine / Volume 50 / Issue 16 / December 2020
- Published online by Cambridge University Press:
- 19 August 2019, p. 2816
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Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis
- Yin Wu, Brooke Levis, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Jill Boruff, Pim Cuijpers, Simon Gilbody, John P.A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Yeates Conwell, Janneke M. de Man-van Ginkel, Jesse R. Fann, Felix H. Fischer, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, Patricia A. Harrison, Martin Härter, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Yunxin Kwan, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Anthony McGuire, Sherina Mohd-Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Katrin Reuter, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Henk C. van Weert, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Andrea Benedetti, Brett D. Thombs
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- Journal:
- Psychological Medicine / Volume 50 / Issue 8 / June 2020
- Published online by Cambridge University Press:
- 12 July 2019, pp. 1368-1380
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Background
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
MethodsWe conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
ConclusionsPHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews
- Brooke Levis, Andrea Benedetti, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Matthew J. Chiovitti, Tatiana A. Sanchez, Pim Cuijpers, Simon Gilbody, John P. A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Russell J. Steele, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Anna Beraldi, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Neerja Chowdhary, Kerrie Clover, Yeates Conwell, Janneke M. de Man-van Ginkel, Jaime Delgadillo, Jesse R. Fann, Felix H. Fischer, Benjamin Fischler, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, John Hambridge, Patricia A. Harrison, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Khalida Ismail, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Laura Marsh, Anthony McGuire, Sherina Mohd Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Christina M. van der Feltz-Cornelis, Henk C. van Weert, Paul A. Vöhringer, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Yuying Zhang, Brett D. Thombs
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- Journal:
- The British Journal of Psychiatry / Volume 212 / Issue 6 / June 2018
- Published online by Cambridge University Press:
- 02 May 2018, pp. 377-385
- Print publication:
- June 2018
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Background
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
MethodData collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
ResultsA total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
ConclusionsThe MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.