Publications by authors named "Paola Dazzan"

213 Publications

Self-guided Cognitive Behavioral Therapy Apps for Depression: Systematic Assessment of Features, Functionality, and Congruence With Evidence.

J Med Internet Res 2021 07 30;23(7):e27619. Epub 2021 Jul 30.

Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.

Background: Mental health disorders affect 1 in 10 people globally, of whom approximately 300 million are affected by depression. At least half of the people affected by depression remain untreated. Although cognitive behavioral therapy (CBT) is an effective treatment, access to mental health specialists, habitually challenging, has worsened because of the COVID-19 pandemic. Internet-based CBT is an effective and feasible strategy to increase access to treatment for people with depression. Mental health apps may further assist in facilitating self-management for people affected by depression; however, accessing the correct app may be cumbersome given the large number and wide variety of apps offered by public app marketplaces.

Objective: This study aims to systematically assess the features, functionality, data security, and congruence with evidence of self-guided CBT-based apps targeting users affected by depression that are available in major app stores.

Methods: We conducted a systematic assessment of self-guided CBT-based apps available in Google Play and the Apple App Store. Apps launched or updated since August 2018 were identified through a systematic search in the 42matters database using CBT-related terms. Apps meeting the inclusion criteria were downloaded and assessed using a Samsung Galaxy J7 Pro (Android 9) and iPhone 7 (iOS 13.3.1). Apps were appraised using a 182-question checklist developed by the research team, assessing their general characteristics, technical aspects and quality assurance, and CBT-related features, including 6 evidence-based CBT techniques (ie, psychoeducation, behavioral activation, cognitive restructuring, problem solving, relaxation, and exposure for comorbid anxiety) as informed by a CBT manual, CBT competence framework, and a literature review of internet-based CBT clinical trial protocols. The results were reported as a narrative review using descriptive statistics.

Results: The initial search yielded 3006 apps, of which 98 met the inclusion criteria and were systematically assessed. There were 20 well-being apps; 65 mental health apps, targeting two or more common mental health disorders, including depression; and 13 depression apps. A total of 28 apps offered at least four evidence-based CBT techniques, particularly depression apps. Cognitive restructuring was the most common technique, offered by 79% (77/98) of the apps. Only one-third of the apps offered suicide risk management resources, whereas 17% (17/98) of the apps offered COVID-19-related information. Although most apps included a privacy policy, only a third of the apps presented it before account creation. In total, 82% (74/90) of privacy policies stated sharing data with third-party service providers. Half of the app development teams included academic institutions or health care providers.

Conclusions: Only a few self-guided CBT-based apps offer comprehensive CBT programs or suicide risk management resources. Sharing of users' data is widespread, highlighting shortcomings in health app market governance. To fulfill their potential, self-guided CBT-based apps should follow evidence-based clinical guidelines, be patient centered, and enhance users' data security.
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http://dx.doi.org/10.2196/27619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367167PMC
July 2021

Maternal perceived bonding towards the infant and parenting stress in women at risk of postpartum psychosis with and without a postpartum relapse.

J Affect Disord 2021 Nov 5;294:210-219. Epub 2021 Jun 5.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RX, UK; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.

Background: Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. However, there is little research on maternal bonding towards the infant and parenting stress in this clinical population.

Methods: We investigated maternal bonding during pregnancy and post-partum in 75 women: 46 at risk of PP (AR), because of a DSM-IV diagnosis of bipolar disorder, schizoaffective disorder or previous PP, and 29 healthy controls. Of the AR women, 19 developed a psychiatric relapse within 4 weeks' post-partum (AR-unwell), while 27 remained symptom-free (AR-well). We investigated childhood maltreatment, parenting stress and psychiatric symptoms as potential predictors of maternal bonding.

Results: In pregnancy, AR-unwell women reported a more negative affective experience towards their infants than AR-well women (d = 0.87, p = .001), while postnatally there was no significant difference in bonding. In contrast, AR women as a group reported a more negative affective experience than HC postnatally (d = 0.69, p = .002; d = 0.70, p = .010), but not antenatally. Parenting stress and psychiatric symptoms significantly predicted less optimal postnatal bonding (b = -0.10, t = -4.29, p < .001; b = -0.37, t = -4.85, p < .001) but only psychiatric symptoms explained the difference in bonding between AR and HC (b = -1.18, 95% BCa CI [-2.70,-0.04]).

Limitations: A relatively small sample size precluded a more in-depth investigation of underlying pathways.

Conclusion: This study provides new information on maternal bonding in women at risk of PP, and particularly in those that do and do not develop a postpartum relapse. The results suggest that improving maternal symptoms and parenting stress in the perinatal period in women at risk of PP could also have positive effects on bonding.
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http://dx.doi.org/10.1016/j.jad.2021.05.076DOI Listing
November 2021

Neurocognitive Measures of Self-blame and Risk Prediction Models of Recurrence in Major Depressive Disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jun 25. Epub 2021 Jun 25.

Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Service for Affective Disorders, South London and Maudsley NHS Foundation Trust, London, United Kingdom; Cognitive and Behavioral Neuroscience Unit, D'Or Institute for Research and Education, Rio de Janeiro, Brazil. Electronic address:

Background: Overgeneralized self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder and prompt specific actions (i.e., action tendencies), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, maladaptive action tendencies (feeling like hiding and feeling like creating a distance from oneself) and an overgeneralized perception of control are characteristic of major depressive disorder, even after remission of symptoms. Here, we probed the potential of this cognitive signature, and its combination with previously employed functional magnetic resonance imaging (fMRI) measures, to predict individual recurrence risk. For this purpose, we developed a user-friendly hybrid machine/statistical learning tool, which we make freely available.

Methods: A total of 52 medication-free patients with remitted major depressive disorder, who had completed the action tendencies task and our self-blame fMRI task at baseline, were followed up clinically over 14 months to determine recurrence. Prospective prediction models included baseline maladaptive self-blame-related action tendencies and anterior temporal fMRI connectivity patterns across a set of frontolimbic a priori regions of interest, as well as including established clinical and standard psychological predictors. Prediction models used elastic net regularized logistic regression with nested 10-fold cross-validation.

Results: Cross-validated discrimination was highly promising (area under the receiver-operating characteristic curve ≥ 0.86), and positive predictive values over 80% were achieved when including fMRI in multimodal models, but only up to 71% (area under the receiver-operating characteristic curve ≤ 0.74) when solely relying on cognitive and clinical measures.

Conclusions: This study shows the high potential of multimodal signatures of self-blaming biases to predict recurrence risk at an individual level and calls for external validation in an independent sample.
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http://dx.doi.org/10.1016/j.bpsc.2021.06.010DOI Listing
June 2021

Childhood and Adulthood Severe Stressful Experiences and Biomarkers Related to Glucose Metabolism: A Possible Association?

Front Psychiatry 2021 14;12:629137. Epub 2021 May 14.

Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

No study investigated the association between stress exposure in different stages of life and metabolic dysfunction. We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals. We used the Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and a modified version of the Life Events Scale to define exposure to stress, according to four categories: no exposure to childhood trauma (CT) nor to stressful life events (SLEs) (46%), only to CT (25%), only to SLEs (21%), to both (8%). We found that c-peptide ( = 0.006) and insulin ( = 0.002) levels differed among the four categories: 0.77 ng/ml (SD 0.27) and 0.21 ng/ml (SD 0.06) for none, 0.77 (SD 0.37) and 0.20 (SD 0.08) for only SLEs, 0.88 (SD 0.39) and 0.27 (SD 0.12) for only CT, 1.33 (SD 0.57) and 0.40 (SD 0.28) for both, respectively. The highest levels of biomarkers were found in subjects exposed to both CT and SLEs. Our preliminary results seem to suggest that CT might be specifically associated with a dysfunction of glucose metabolism, which might increase the risk of poorer health outcomes in adulthood. This association seems to be even stronger in individuals additionally exposed to SLEs in adulthood. In conclusion, if confirmed in other studies, subjects exposed to both CT and SLEs appear the most vulnerable individuals, for whom preventative interventions, such as healthy lifestyle education programs, might ameliorate the risk of developing metabolic abnormalities.
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http://dx.doi.org/10.3389/fpsyt.2021.629137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160252PMC
May 2021

Mother-infant interaction in women with depression in pregnancy and in women with a history of depression: the Psychiatry Research and Motherhood - Depression (PRAM-D) study.

BJPsych Open 2021 May 25;7(3):e100. Epub 2021 May 25.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.

Background: Little is known about the effects of depression before birth on the quality of the mother-infant interaction.

Aims: To understand whether depression, either in pregnancy or in lifetime before pregnancy, disrupts postnatal mother-infant interactions.

Method: We recruited 131 pregnant women (51 healthy, 52 with major depressive disorder (MDD) in pregnancy, 28 with a history of MDD but healthy pregnancy), at 25 weeks' gestation. MDD was confirmed with the Structured Clinical Interview for DSM-IV Disorders. Neonatal behaviour was assessed at 6 days with the Neonatal Behavioural Assessment Scale, and mother-infant interaction was assessed at 8 weeks and 12 months with the Crittenden CARE-Index.

Results: At 8 weeks and 12 months, dyads in the depression and history-only groups displayed a reduced quality of interaction compared with healthy dyads. Specifically, at 8 weeks, 62% in the depression group and 56% in the history-only group scored in the lowest category of dyadic synchrony (suggesting therapeutic interventions are needed), compared with 37% in the healthy group (P = 0.041); 48% and 32%, respectively, scored the same at 12 months, compared with 14% in the healthy group (P = 0.003). At 6 days, neonates in the depression and history-only groups exhibited decreased social-interactive behaviour, which, together with maternal socioeconomic difficulties, was also predictive of interaction quality, whereas postnatal depression was not.

Conclusions: Both antenatal depression and a lifetime history of depression are associated with a decreased quality of mother-infant interaction, irrespective of postnatal depression. Clinicians should be aware of this, as pregnancy provides an opportunity for identification and intervention to support the developing relationship.
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http://dx.doi.org/10.1192/bjo.2021.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167851PMC
May 2021

Sex hormones and immune system: A possible interplay in affective disorders? A systematic review.

J Affect Disord 2021 07 24;290:1-14. Epub 2021 Apr 24.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, UK; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley NHS Foundation Trust and King's College London, London, UK.

Background: Sex hormones and the immune system may play a key role in sex differences in affective disorders. The understanding of their interplay may lead to the detection of new sex-specific tailored therapeutic approaches. The aim of this systematic review is to summarise the evidence supporting a possible association between sex hormones and inflammatory biomarkers in people with affective disorders.

Methods: A systematic search of the literature published until January 2021 was conducted on PubMed database. The initial search identified a total of 1259 studies; 20 studies investigating inflammatory biomarkers and sex hormones in patients exhibiting depressive symptoms were included: 10 studies focused on patients with affective disorders, and 10 studies focused on women in menopause or in the post-partum period exhibiting depressive symptoms.

Results: Testosterone and exogenous female sex hormones may play protective roles through their modulation of the immune system, respectively, in male patients with bipolar disorder and in peri-/post-menopausal women with depression.

Limitations: The main limitations are the paucity of studies investigating both sex hormones and immune biomarkers, the lack of statistical analyses exploring specifically the association between these two classes of biomarkers, and the great heterogeneity between the participants' samples in the studies.

Conclusion: This review highlights the need to investigate the interplay between sex hormones and immune system in affective disorders. The inconsistent or incomplete evidence may be improved by studies in patients with moderate-high inflammatory levels that specifically evaluate the relationship between sex hormones and the immune system.
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http://dx.doi.org/10.1016/j.jad.2021.04.035DOI Listing
July 2021

Altered dynamics of the prefrontal networks are associated with the risk for postpartum psychosis: a functional magnetic resonance imaging study.

Transl Psychiatry 2021 05 12;11(1):238. Epub 2021 May 12.

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.

Postpartum psychosis (PP) is a severe mental disorder that affects women in the first few weeks after delivery. To date there are no biomarkers that distinguish which women at risk (AR) develop a significant psychiatric relapse postpartum. While altered brain connectivity may contribute to the risk for psychoses unrelated to the puerperium, this remains unexplored in PP. We followed up 32 AR and 27 healthy (HC) women from pregnancy to 8-week postpartum. At this point, we classified women as AR-unwell (n = 15) if they had developed a psychiatric relapse meeting DSM-IV diagnostic criteria, or impacting on daily functioning and requiring treatment, or AR-well (n = 17) if they remained asymptomatic. Women also underwent an fMRI scan at rest and during an emotional-processing task, to study within- and between-networks functional connectivity. Women AR, and specifically those in the AR-well group, showed increased resting connectivity within an executive network compared to HC. During the execution of the emotional task, women AR also showed decreased connectivity in the executive network, and altered emotional load-dependent connectivity between executive, salience, and default-mode networks. AR-unwell women particularly showed increased salience network-dependent modulation of the default-mode and executive network relative to AR-well, who showed greater executive network-dependent modulation of the salience network. Our finding that the executive network and its interplay with other brain networks implicated in goal-directed behavior are intrinsically altered suggest that they could be considered neural phenotypes for postpartum psychosis and help advance our understanding of the pathophysiology of this disorder.
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http://dx.doi.org/10.1038/s41398-021-01351-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113224PMC
May 2021

Risk factors for postpartum relapse in women at risk of postpartum psychosis: The role of psychosocial stress and the biological stress system.

Psychoneuroendocrinology 2021 06 3;128:105218. Epub 2021 Apr 3.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. Electronic address:

Background: Postpartum psychosis is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high for women with a history of bipolar disorder, schizoaffective disorder or those who have suffered a previous episode of postpartum psychosis. Whilst there is a lot of evidence linking stress to psychosis unrelated to childbirth, the role of stress in the onset of postpartum psychosis has not been fully investigated.

Methods: A prospective longitudinal study of 112 pregnant women, 51 at risk of postpartum psychosis because of a DSM-IV diagnosis of bipolar disorder (n = 41), schizoaffective disorder (n = 6) or a previous postpartum psychosis (n = 4) and 61 healthy women with no past or current DSM-IV diagnosis and no family history of postpartum psychosis. Women were followed up from the third trimester of pregnancy to 4 weeks' post partum. Women at risk who had a psychiatric relapse in the first 4 weeks' post partum (AR-unwell) (n = 22), were compared with those at risk who remained well (AR-well) (n = 29) on measures of psychosocial stress (severe childhood maltreatment and stressful life events) and biological stress (cortisol and inflammatory biomarkers).

Results: Logistic regression analyses revealed that severe childhood maltreatment (OR = 4.9, 95% CI 0.5-49.2) and higher daily cortisol in the third trimester of pregnancy (OR=3.7, 95% CI 1.2-11.6) predicted psychiatric relapse in the first 4 weeks' post partum in women at risk of postpartum psychosis after adjusting for clinical and sociodemographic covariates.

Conclusion: The current study provides evidence for the role of psychosocial stress and the biological stress system in the risk of postpartum relapse in women at risk of postpartum psychosis.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105218DOI Listing
June 2021

Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses.

Schizophr Bull 2021 Apr 14. Epub 2021 Apr 14.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = -2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.
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http://dx.doi.org/10.1093/schbul/sbab035DOI Listing
April 2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Transl Psychiatry 2021 03 22;11(1):182. Epub 2021 Mar 22.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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http://dx.doi.org/10.1038/s41398-021-01213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307PMC
March 2021

The Role of Peripheral Inflammation in Clinical Outcome and Brain Imaging Abnormalities in Psychosis: A Systematic Review.

Front Psychiatry 2021 19;12:612471. Epub 2021 Feb 19.

Department of Psychological Medicine, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom.

Promising research investigating the association between inflammatory biomarkers and response to antipsychotic and/or adjunctive therapy, observed by improvement in psychiatric assessment, is emerging. Increased inflammation has been suggested to contribute to higher severity of symptoms/treatment resistance through the effects that this has on brain structure and function. The present systematic review aims to clarify the potential role of peripheral inflammatory markers as predictors of clinical outcomes and their association with neuroimaging markers in patients with psychosis. Systematic searches of the literature using the databases PsychInfo, OVID Medline, and Embase were conducted to collate studies investigating the association of inflammatory biomarkers with clinical outcome in patients with psychotic disorders and studies examining the relationships between inflammatory biomarkers and neuroimaging data. Seventeen studies on predictors of clinical outcome and 14 on associations between neuroimaging data and inflammatory biomarkers in psychosis were identified, and risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The main inflammatory markers associated with clinical outcome in psychosis were interleukin (IL)-6, IL-10, and C-reactive protein (CRP). High levels of CRP and IL-6 were associated with worse clinical outcome and deterioration of symptoms over time; in contrast, increased levels of IL-10 were associated with greater symptoms improvement. Smaller hippocampal volume and reduced cortical thickness were the main neuroimaging markers associated with increased peripheral inflammation. The heterogeneity across the studies (i.e., treatments strategies, duration) suggests that potential prediction power of inflammatory biomarkers could partially depend on the methodologies, supported by the overall NOS ratings of the studies. Future studies may need to consider whether a combination of these inflammatory and neuroimaging markers could further improve our ability of predicting clinical outcome in patients with psychosis.
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http://dx.doi.org/10.3389/fpsyt.2021.612471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933584PMC
February 2021

Schizophrenia during pregnancy.

Authors:
Paola Dazzan

Curr Opin Psychiatry 2021 05;34(3):238-244

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Purpose Of Review: A diagnosis of schizophrenia has significant implications for women of childbearing age, pregnant or considering a pregnancy, ranging from sexual health, psychopharmacological treatment, to the occurrence of negative pregnancy and foetal outcomes. We provide a short narrative review of recent papers focusing on these issues.

Recent Findings: Although pregnancy rates have been increasing in women with a diagnosis of schizophrenia, they also tend to have altogether fewer pregnancies and fewer live births than women without this diagnosis, and also higher rates of induced abortions.Use of antipsychotics in pregnancy has also increased, and evidence suggests lack of significant contraindications for their use in this period. However, drug levels monitoring may be recommended across the three trimesters, as levels may change in relation to pregnancy-related physiology.Monitoring of physical health is an increasingly crucial issue, given higher risk of gestational diabetes, negative obstetric and infant outcomes in these women.

Summary: There is an urgent need to generate valid and reproducible research that could help implement appropriate treatment protocols and relapse-prevention approaches, and interventions based on strong pharmaceutical targets for the benefit of pregnant women with a diagnosis of schizophrenia, their families and their children.
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http://dx.doi.org/10.1097/YCO.0000000000000706DOI Listing
May 2021

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Hum Brain Mapp 2021 Feb 21. Epub 2021 Feb 21.

Center for Neuroimaging, Genetics and Genomics, School of Psychology, NUI Galway, Galway, Ireland.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
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http://dx.doi.org/10.1002/hbm.25354DOI Listing
February 2021

Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis.

Biol Psychiatry 2021 07 24;90(1):9-15. Epub 2020 Nov 24.

Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, University College London, London, United Kingdom.

Background: When psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear.

Methods: Sera from 387 patients with FEP (duration of psychosis <2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride.

Results: At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p = .031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects.

Conclusions: These data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy.
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http://dx.doi.org/10.1016/j.biopsych.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191702PMC
July 2021

Rethinking the course of psychotic disorders: modelling long-term symptom trajectories.

Psychol Med 2021 Feb 4:1-10. Epub 2021 Feb 4.

ESRC Centre for Society and Mental Health, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, UK.

Background: The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach.

Method: AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time.

Results: We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory.

Conclusion: Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.
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http://dx.doi.org/10.1017/S0033291720004705DOI Listing
February 2021

Scaling-up Health-Arts Programmes: the largest study in the world bringing arts-based mental health interventions into a national health service.

BJPsych Bull 2021 Feb;45(1):32-39

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.

The Scaling-up Health-Arts Programme: Implementation and Effectiveness Research (SHAPER) project is the world's largest hybrid study on the impact of the arts on mental health embedded into a national healthcare system. This programme, funded by the Wellcome Trust, aims to study the impact and the scalability of the arts as an intervention for mental health. The programme will be delivered by a team of clinicians, research scientists, charities, artists, patients and healthcare professionals in the UK's National Health Service (NHS) and the community, spanning academia, the NHS and the charity sector. SHAPER consists of three studies - Melodies for Mums, Dance for Parkinson's, and Stroke Odysseys - which will recruit over 800 participants, deliver the interventions and draw conclusions on their clinical impact, implementation effectiveness and cost-effectiveness. We hope that this work will inspire organisations and commissioners in the NHS and around the world to expand the remit of social prescribing to include evidence-based arts interventions.
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http://dx.doi.org/10.1192/bjb.2020.122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058867PMC
February 2021

Are attenuated positive symptoms and cortisol levels associated?

Schizophr Res 2021 02 26;228:621-623. Epub 2020 Nov 26.

Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Kildegårdsvej 28, opg. 15, Hellerup, Denmark.

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http://dx.doi.org/10.1016/j.schres.2020.11.024DOI Listing
February 2021

Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment.

Brain Behav Immun 2021 01 5;91:498-504. Epub 2020 Nov 5.

Institute for Mental Health, University of Birmingham, UK; Forward Thinking Birmingham, Birmingham Women's and Children's Hospital NHS Foundation Trust, UK.

Background: Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline.

Methods: We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients.

Results: Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group.

Discussion: IL-6 may have some specificity to depression in early schizophrenia. TNF-α may be an indicator of immune dysfunction relevant to negative symptoms, and our longitudinal findings add to this evidence. However, minocycline continues to show very little promise as a treatment for any symptom dimension of early schizophrenia.
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http://dx.doi.org/10.1016/j.bbi.2020.10.026DOI Listing
January 2021

Predicting onset of early- and late-treatment resistance in first-episode schizophrenia patients using advanced shrinkage statistical methods in a small sample.

Psychiatry Res 2020 12 21;294:113527. Epub 2020 Oct 21.

Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.

Evidence suggests there are two treatment-resistant schizophrenia subtypes (i.e. early treatment resistant (E-TR) and late-treatment resistant (L-TR)). We aimed to develop prediction models for estimating individual risk for these outcomes by employing advanced statistical shrinkage methods. 239 first-episode schizophrenia (FES) patients were followed-up for approximately 5 years after first presentation to psychiatric services; of these, n=56 (25.2%) were defined as E-TR and n=24 (12.6%) were defined as L-TR. Using known risk factors for poor schizophrenia outcomes, we developed prediction models for E-TR and L-TR using LASSO and RIDGE logistic regression models. Models' internal validation was performed employing Harrell's optimism-correction with repeated cross-validation; their predictive accuracy was assessed through discrimination and calibration. Both LASSO and RIDGE models had high discrimination, good calibration. While LASSO had moderate sensitivity for estimating an individual risk for E-TR and L-TR, sensitivity estimated for RIDGE model for these outcomes was extremely low, which was due to having a very large estimated optimism. Although it was possible to discriminate with sufficient accuracy who would meet criteria for E-TR and L-TR during the 5-year follow-up after first contact with mental health services for schizophrenia, further work is necessary to improve sensitivity for these models.
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http://dx.doi.org/10.1016/j.psychres.2020.113527DOI Listing
December 2020

Cerebellar hypoactivation is associated with impaired sensory integration in schizophrenia.

J Abnorm Psychol 2021 Jan 19;130(1):102-111. Epub 2020 Oct 19.

Neuropsychology and Applied Cognitive Neuroscience Laboratory.

To clarify the involvement of the cerebellum in impaired sensory integration in patients with schizophrenia, 52 first-episode patients with schizophrenia and 52 age- and sex-matched healthy controls underwent a verified sensory integration imaging task to examine the whole-brain dysfunction underlying impaired sensory integration. The familiality of cerebellar activation when integrating sensory stimuli was investigated in 25 siblings of the patients with schizophrenia, while the heritability of cerebellar activation was estimated in 56 monozygotic twins and 56 dizygotic twins. In addition, the functional connectivity between the cerebellum and the remaining regions of the whole brain was explored with psychophysiological interaction analysis. Relative to healthy controls, patients with schizophrenia showed reduced cerebellar activation when performing the sensory integration task in the whole-brain analysis. This reduced cerebellar activation was also found in the siblings of patients with schizophrenia, but to a lesser extent compared with schizophrenia patients. Cerebellar activation during sensory integration was also found to be significantly heritable. Furthermore, dysconnectivity within the cerebellum was found in patients with schizophrenia when integrating auditory and visual stimuli. These findings highlight the role of cerebellar dysfunction in the pathophysiology of schizophrenia symptoms and its potential role as an endophenotype of schizophrenia spectrum disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/abn0000636DOI Listing
January 2021

Symptom Remission and Brain Cortical Networks at First Clinical Presentation of Psychosis: The OPTiMiSE Study.

Schizophr Bull 2021 03;47(2):444-455

Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark.

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus facilitate stratification and individualized treatment of patients with schizophrenia. We used magnetic resonance imaging at baseline to examine brain regional and network correlates of subsequent symptomatic remission in 167 medication-naïve or minimally treated patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder entering a three-phase trial, at seven sites. Patients in remission at the end of each phase were randomized to treatment as usual, with or without an adjunctive psycho-social intervention for medication adherence. The final follow-up visit was at 74 weeks. A total of 108 patients (70%) were in remission at Week 4, 85 (55%) at Week 22, and 97 (63%) at Week 74. We found no baseline regional differences in volumes, cortical thickness, surface area, or local gyrification between patients who did or did not achieved remission at any time point. However, patients not in remission at Week 74, at baseline showed reduced structural connectivity across frontal, anterior cingulate, and insular cortices. A similar pattern was evident in patients not in remission at Week 4 and Week 22, although not significantly. Lack of symptom remission in first-episode psychosis is not associated with regional brain alterations at illness onset. Instead, when the illness becomes a stable entity, its association with the altered organization of cortical gyrification becomes more defined.
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http://dx.doi.org/10.1093/schbul/sbaa115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965060PMC
March 2021

Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis.

Hum Brain Mapp 2021 02 13;42(2):439-451. Epub 2020 Oct 13.

Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

The ability to identify biomarkers of psychosis risk is essential in defining effective preventive measures to potentially circumvent the transition to psychosis. Using samples of people at clinical high risk for psychosis (CHR) and Healthy controls (HC) who were administered a task fMRI paradigm, we used a framework for labelling time windows of fMRI scans as 'integrated' FC networks to provide a granular representation of functional connectivity (FC). Periods of integration were defined using the 'cartographic profile' of time windows and k-means clustering, and sub-network discovery was carried out using Network Based Statistics (NBS). There were no network differences between CHR and HC groups. Within the CHR group, using integrated FC networks, we identified a sub-network negatively associated with longitudinal changes in the severity of psychotic symptoms. This sub-network comprised brain areas implicated in bottom-up sensory processing and in integration with motor control, suggesting it may be related to the demands of the fMRI task. These data suggest that extracting integrated FC networks may be useful in the investigation of biomarkers of psychosis risk.
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http://dx.doi.org/10.1002/hbm.25235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775992PMC
February 2021

Diagnostic stability and outcome after first episode psychosis.

J Ment Health 2021 Feb 22;30(1):104-112. Epub 2020 Sep 22.

King's College London, Health Services and Population Research Department, Institute of Psychiatry, Psychology & Neuroscience, London, UK.

Background: Individuals diagnosed with schizophrenia are often assigned other psychiatric diagnoses during their lives. The significance of changing diagnosis has not been widely studied.

Aims: Our aim was to examine the association between diagnostic change and later outcome.

Methods: Individuals' diagnostic history, clinical and social outcomes were extracted from the AESOP-10 study, a 10-year follow-up of first episode psychosis cases. The association between outcome and different patterns of diagnosis over time were assessed using linear or logistic regression.

Results: Individuals always diagnosed with schizophrenia ( = 136) had worse clinical and social outcomes at follow-up than those never diagnosed with schizophrenia ( = 163), being more likely to be symptomatic, unemployed, single, and socially isolated. There was no difference in outcome between individuals always diagnosed with schizophrenia and those changing to a diagnosis of schizophrenia ( = 60), and no difference in outcome between individuals never diagnosed with schizophrenia, and those changing from a diagnosis of schizophrenia ( = 44).

Conclusions: Individuals always and never diagnosed with schizophrenia had different outcomes. In cases of diagnostic instability participants had similar outcomes to those always assigned the diagnosis they changed to irrespective of initial diagnosis.
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http://dx.doi.org/10.1080/09638237.2020.1818191DOI Listing
February 2021

COVID-19 experience among Brasil's indigenous people.

Rev Assoc Med Bras (1992) 2020 Jul 24;66(7):861-863. Epub 2020 Aug 24.

School of Life Course Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

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http://dx.doi.org/10.1590/1806-9282.66.7.861DOI Listing
July 2020

Threat, hostility and violence in childhood and later psychotic disorder: population-based case-control study.

Br J Psychiatry 2020 10;217(4):575-582

Institute of Psychiatry, Psychology & Neuroscience, King's College London; and Economic and Social Research Council (ESRC) Centre for Society and Mental Health, King's College London, UK.

Background: A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.

Aims: Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.

Method: CAPsy is population-based first-episode psychosis case-control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.

Results: We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.

Conclusions: Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.
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http://dx.doi.org/10.1192/bjp.2020.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525109PMC
October 2020

A GABA Interneuron Deficit Model of the Art of Vincent van Gogh.

Front Psychiatry 2020 13;11:685. Epub 2020 Jul 13.

Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.

Vincent van Gogh was one of the most influential artists of the Western world, having shaped the post-impressionist art movement by shifting its boundaries forward into abstract expressionism. His distinctive style, which was not valued by the art-buying public during his lifetime, is nowadays one of the most sought after. However, despite the great deal of attention from academic and artistic circles, one important question remains open: was van Gogh's original style a visual manifestation distinct from his troubled mind, or was it in fact a by-product of an impairment that resulted from the psychiatric illness that marred his entire life? In this paper, we use a previously published multi-scale model of brain function to piece together a number of disparate observations about van Gogh's life and art. In particular, we first quantitatively analyze the brushwork of his large production of self-portraits using the image autocorrelation and demonstrate a strong association between the contrasts in the paintings, the occurrence of psychiatric symptoms, and his simultaneous use of absinthe-a strong liquor known to affect gamma aminobutyric acid (GABA) alpha receptors. Secondly, we propose that van Gogh suffered from a defective function of parvalbumin interneurons, which seems likely given his family history of schizophrenia and his addiction to substances associated with GABA action. This could explain the need for the artist to increasingly amplify the contrasts in his brushwork as his disease progressed, as well as his tendency to merge esthetic and personal experiences into a new form of abstraction.
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http://dx.doi.org/10.3389/fpsyt.2020.00685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370815PMC
July 2020

Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study.

Schizophr Bull 2021 01;47(1):118-127

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Minor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches.
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http://dx.doi.org/10.1093/schbul/sbaa089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824991PMC
January 2021

Rasch analysis of the PANSS negative subscale and exploration of negative symptom trajectories in first-episode schizophrenia - data from the OPTiMiSE trial.

Psychiatry Res 2020 07 18;289:112970. Epub 2020 Apr 18.

Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Nordstjernevej 41, Glostrup, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.

The observed heterogeneity in negative symptom treatment response may be partly attributable to inadequate measurement tools or limitations in methods of analysis. Previous Item Response Theory models of the Positive and Negative Syndrome Scale (PANSS) have only examined samples of chronic patients and with mixed results. We examined the scalability of the negative subscale embedded in the PANSS and subsequently explored negative symptom trajectories across four weeks of amisulpride treatment. Data were derived from the OPTiMiSE trial comprising 446 patients with first-episode schizophrenia or schizophreniform disorder. Using the Rasch Model to examine psychometric properties of the PANSS negative subscale, we found that the composite score across items was not an adequate measure of negative symptom severity. Consequently, we chose an exploratory statistical approach involving Principal Component Analysis which yielded one significant component clustering into two significant symptom trajectories: 1) Subtle but constant decrease in negative symptom severity (N = 323; 72%), and 2) symptom instability across visits (N = 19; 4%). Explorative analytic methods as presented here may pave the way for more efficient and sensitive methods of analyzing negative symptom response in research and in clinical practice.
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http://dx.doi.org/10.1016/j.psychres.2020.112970DOI Listing
July 2020

Rasch analysis of the PANSS negative subscale and exploration of negative symptom trajectories in first-episode schizophrenia - data from the OPTiMiSE trial.

Psychiatry Res 2020 07 18;289:112970. Epub 2020 Apr 18.

Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Nordstjernevej 41, Glostrup, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.

The observed heterogeneity in negative symptom treatment response may be partly attributable to inadequate measurement tools or limitations in methods of analysis. Previous Item Response Theory models of the Positive and Negative Syndrome Scale (PANSS) have only examined samples of chronic patients and with mixed results. We examined the scalability of the negative subscale embedded in the PANSS and subsequently explored negative symptom trajectories across four weeks of amisulpride treatment. Data were derived from the OPTiMiSE trial comprising 446 patients with first-episode schizophrenia or schizophreniform disorder. Using the Rasch Model to examine psychometric properties of the PANSS negative subscale, we found that the composite score across items was not an adequate measure of negative symptom severity. Consequently, we chose an exploratory statistical approach involving Principal Component Analysis which yielded one significant component clustering into two significant symptom trajectories: 1) Subtle but constant decrease in negative symptom severity (N = 323; 72%), and 2) symptom instability across visits (N = 19; 4%). Explorative analytic methods as presented here may pave the way for more efficient and sensitive methods of analyzing negative symptom response in research and in clinical practice.
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http://dx.doi.org/10.1016/j.psychres.2020.112970DOI Listing
July 2020
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