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13. Neural correlates of treatment in depression and potential predictors of diagnosis and clinical response

Author

Sankar, Anjali, Fu, Cynthia, and Costafreda, Sergi

Subjects
150
Abstract

The works presented in this thesis examine the neural effects of treatment on different features of depression, such as affective biases, working memory impairments and dysfunctional thinking. The thesis opens with a review of longitudinal studies that examined the effects of antidepressants and psychological therapies on the neural correlates of affective and cognitive processing. Motivated by the paucity in the number of fMRI studies that examined psychotherapy in depression, Chapter 2 examines the effects of Cognitive Behavioural Therapy (CBT) on dysfunctional thinking in depression. In Chapter 3, the effects of a dual acting serotonin norepinephrine reuptake inhibitor, duloxetine, on affective biases are examined using implicit affective paradigms comprising happy and sad facial expressions. Chapter 4 investigates the neural effects of duloxetine on working memory in depression utilizing a modified version of the Sternberg Working Memory Task. Another key focus in the thesis is to examine the potential of structural neuroimaging data to identify depression and predict clinical remission using machine learning algorithms in a sample of wide ethnic diversity from the community. Findings from this study are presented in Chapter 5. Overall, the results showed antidepressant treatment related increases in posterior cingulate during sad facial effect processing, consistent with preliminary findings that show increases in this region with antidepressants that potentiate the noradrenergic systems. The neural correlates of working memory, on the other hand, showed a significant group by time interaction during the rehearsal phase, such that there was a tendency for reductions in brain activations at the follow up scan compared to baseline in healthy controls in a network of brain areas extending from the prefrontal, to the cingulate, temporal and cerebellar regions, while no change was observed in patients. The tendency for decreased activations in controls in the follow up scan is perhaps indicative of less recruitment of these regions with increased familiarity with the task, while no change in activation in patients may reflect persistent recruitment of regions associated with working memory to maintain task performance. In the CBT study, an interaction effect was found in the left parahippocampal gyrus, which showed less attenuation in patients relative to controls at the follow up scan, perhaps reflecting an improvement in dysfunctional thinking with CBT with some persistent vulnerability. Investigation of neuroimagingbased biomarkers in depression indicated that structural neuroanatomy combining white and grey matter distinguished patients from controls at the highest accuracy of 81% with the most stable pattern being at around 70%. In contrast, the whole brain structural correlates of depression showed limited potential as a prognostic marker. These findings suggest some distinct neural effects of treatment on cognitive and affective processing and provide preliminary evidence to indicate that identification of depression is possible within a multi-ethnic group from the general community.

Published
2015

18. The relation between neocortical serotonin 2A receptor binding and neuroticism in the risk for developing depression in healthy individuals: a BrainDrugs study

Author

Sankar, Anjali, primary, Ziersen, Simon, additional, Ozenne, Brice, additional, Dam, Vibeke, additional, Beaman, Emily, additional, Kessing, Lars, additional, Fisher, Patrick, additional, Budtz-Jørgensen, Esben, additional, Knudsen, Gitte, additional, Miskowiak, Kamilla, additional, and Frokjaer, Vibe, additional

Published
2023
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20. Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction

Author

Koehler-Forsberg, Kristin, Dam, Vibeke H., Ozenne, Brice, Sankar, Anjali, Beliveau, Vincent, Landman, Elizabeth B., Larsen, Søren V., Poulsen, Asbjørn S., Ip, Cheng-Teng, Jørgensen, Anders, Meyer, Michal, Stenbaek, Dea S., Eiberg, Hans R. L., Madsen, Jacob, Svarer, Claus, Jorgensen, Martin B., Frokjaer, Vibe G., Knudsen, Gitte M., Koehler-Forsberg, Kristin, Dam, Vibeke H., Ozenne, Brice, Sankar, Anjali, Beliveau, Vincent, Landman, Elizabeth B., Larsen, Søren V., Poulsen, Asbjørn S., Ip, Cheng-Teng, Jørgensen, Anders, Meyer, Michal, Stenbaek, Dea S., Eiberg, Hans R. L., Madsen, Jacob, Svarer, Claus, Jorgensen, Martin B., Frokjaer, Vibe G., and Knudsen, Gitte M.

Abstract

Importance The cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals. Objective To map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state. Design, Setting, and Participants This case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark. Adult participants included antidepressant-free outpatients with a current moderate to severe depressive episode and healthy controls. All participants completed positron emission tomography (PET) scanning with [11C]SB207145 for quantification of brain 5-HT4 receptor binding, but only the patients underwent cognitive testing. Data analyses were performed from January 21, 2020, to April 22, 2022. Main Outcomes and Measures The main study outcome was the group difference in cerebral 5-HT4 receptor binding between patients with MDD and healthy controls. In addition, the association between 5-HT4 receptor binding and verbal memory performance in the patient group was tested. Other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) were assessed as secondary outcomes. Results A total of 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]) were included in the analysis. Patients with current MDD had significantly lower cerebral 5-HT4 receptor binding than healthy controls (−7.0%; 95% CI, −11.2 to −2.7; P = .002). In patients with MDD, there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02). Conclusions and Rel, IMPORTANCE The cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals.OBJECTIVE To map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state.DESIGN, SETTING, AND PARTICIPANTS This case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark. Adult participants included antidepressant-free outpatients with a current moderate to severe depressive episode and healthy controls. All participants completed positron emission tomography (PET) scanning with [C-11]SB207145 for quantification of brain 5-HT4 receptor binding, but only the patients underwent cognitive testing. Data analyses were performed from January 21, 2020, to April 22, 2022.MAIN OUTCOMES AND MEASURES The main study outcome was the group difference in cerebral 5-HT4 receptor binding between patients with MDD and healthy controls. In addition, the association between 5-HT4 receptor binding and verbal memory performance in the patient group was tested. Other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) were assessed as secondary outcomes.RESULTS A total of 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]) were included in the analysis. Patients with current MDD had significantly lower cerebral 5-HT4 receptor binding than healthy controls (-7.0%; 95% CI, -11.2 to -2.7; P = .002). In patients with MDD, there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02).CONCLUSIONS AND RELEVANCE Results of this study show that cerebra

Published
2023

21. Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction

Author

Köhler-Forsberg, Kristin, primary, Dam, Vibeke H., additional, Ozenne, Brice, additional, Sankar, Anjali, additional, Beliveau, Vincent, additional, Landman, Elizabeth B., additional, Larsen, Søren V., additional, Poulsen, Asbjørn S., additional, Ip, Cheng-Teng, additional, Jørgensen, Anders, additional, Meyer, Michal, additional, Stenbæk, Dea S., additional, Eiberg, Hans R. L., additional, Madsen, Jacob, additional, Svarer, Claus, additional, Jørgensen, Martin B., additional, Frokjaer, Vibe G., additional, and Knudsen, Gitte M., additional

Published
2023
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23. Brain grey and white matter structural associations with future suicidal ideation and behaviors in adolescent and young adult females with mood disorders

Author

Colic, Lejla, Villa, Luca M, Dauvermann, Maria R, Van Velzen, Laura S, Sankar, Anjali, Goldman, Danielle A, Panchal, Priyanka, Kim, Jihoon A, Quatrano, Susan, Spencer, Linda, Constable, R Todd, Suckling, John, Goodyer, Ian M, Schmaal, Lianne, Van Harmelen, Anne-Laura, Blumberg, Hilary P, Colic, Lejla [0000-0002-8809-4034], van Velzen, Laura S [0000-0002-6003-5227], and Apollo - University of Cambridge Repository

Subjects
suicidal behaviour, gender, magnetic resonance imaging, adolescence, mood disorder
Abstract

Funder: American Foundation for Suicide Prevention; Id: http://dx.doi.org/10.13039/100001455, Funder: AIM Youth Mental Health Foundation, Funder: For the Love of Travis Foundation, Funder: International Bipolar Foundation, Funder: Interdisciplinary Center of Clinical Research of the Medical Faculty Jena, Funder: Leiden University Social Safety and Resilience program, Funder: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Funder: Klingenstein Third Generation Foundation; Id: http://dx.doi.org/10.13039/100006211, Funder: University of Melbourne Dame Kate Campbell fellowship, Funder: Suicide Prevention Australia; Id: http://dx.doi.org/10.13039/501100019998, BACKGROUND: To reduce suicide in females with mood disorders, it is critical to understand brain substrates underlying their vulnerability to future suicidal ideation and behaviors (SIBs) in adolescence and young adulthood. In an international collaboration, grey and white matter structure was investigated in adolescent and young adult females with future suicidal behaviors (fSB) and ideation (fSI), and without SIBs (fnonSIB). METHODS: Structural (n = 91) and diffusion-weighted (n = 88) magnetic resonance imaging scans at baseline and SIB measures at follow-up on average two years later (standard deviation, SD = 1 year) were assessed in 92 females [age(SD) = 16.1(2.6) years] with bipolar disorder (BD, 28.3%) or major depressive disorder (MDD, 71.7%). One-way analyses of covariance comparing baseline regional grey matter cortical surface area, thickness, subcortical grey volumes, or white matter tensor-based fractional anisotropy across fSB (n = 40, 43.5%), fSI (n = 33, 35.9%) and fnonSIB (n = 19, 20.6%) groups were followed by pairwise comparisons in significant regions (p < 0.05). RESULTS: Compared to fnonSIBs, fSIs and fSBs showed significant decreases in cortical thickness of right inferior frontal gyrus pars orbitalis and middle temporal gyrus, fSIs of left inferior frontal gyrus, pars orbitalis. FSIs and fSBs showed lower fractional anisotropy in left uncinate fasciculus and corona radiata, and fSBs in right uncinate and superior fronto-occipital fasciculi. CONCLUSIONS: The study provides preliminary evidence of grey and white matter alterations in brain regions subserving emotional and behavioral regulation and perceptual processing in adolescent and young adult females with mood disorders with, versus without, future SIBs. Findings suggest potential targets to prevent SIBs in female adolescents and young adults.

Published
2022
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24. Brain grey and white matter structural associations with future suicidal ideation and behaviors in adolescent and young adult females with mood disorders

Author

Colic, Lejla, primary, Villa, Luca M., additional, Dauvermann, Maria R., additional, van Velzen, Laura S., additional, Sankar, Anjali, additional, Goldman, Danielle A., additional, Panchal, Priyanka, additional, Kim, Jihoon A., additional, Quatrano, Susan, additional, Spencer, Linda, additional, Constable, R. Todd, additional, Suckling, John, additional, Goodyer, Ian M., additional, Schmaal, Lianne, additional, van Harmelen, Anne‐Laura, additional, and Blumberg, Hilary P., additional

Published
2022
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25. PREPARATION, CHARACTERIZATION OF CHITOSAN NANOPARTICLES

Author

Sankar, Anjali, Sindhu Ramesh, and Nishitha Arun

Subjects
Biomedical engineering, Chitosan, Chlorhexidine, Endodontics, Irrigant, Nanomedicine, Nanoparticle
Abstract

Introduction The discovery of nanoparticles' unique properties has allowed them to be used in a variety of fields, including bioengineering.Chitosan is a linear polyaminosaccharide made from chitin, the second most prevalent natural biopolymer after cellulose. It can be readily produced into a number of forms that may be tailored to specific applications. The goal of this research was to synthesise chitosan nanoparticles with chlorhexidine and to characterise its properties using FTIR and SEM. Materials and Methods Synthesis and optimization of chitosan nanoparticles followed by Preparation of Nanochitosan with Chlorhexidine solution by adding 50ml of 2% Chlorhexidiene was added to 50 ml of the prepared nano chitosan solution. The resulting solution was sonicated for 10 mins until the solution was clear. The properties of the resultant solution were characterised by using FTIR and SEM. Results The chitosan nanoparticles prepared in the experiment exhibited white powder shape. The SEM micrographs of the nano chitosan with chlorhexidine showed that they were approximately circular and conical shaped nanoparticles of varying sizes. The unmodified chitosan nanoparticles are composed of clusters of nanoparticles with sizes ranging from 10 nm to 80 nm. Conclusion The results show that a novel chitosan nanoparticle was successfully synthesised and characterised. It seems that this nanoparticle like the other chitosan nanoparticles has potential applications as an irrigant having antimicrobial properties, increased depth of penetration into the dentinal tubules and removal of the smear layer in the field of endodontics.

Published
2022
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26. DIAGNOSTIC ACCURACY OF CONE BEAM COMPUTED TOMOGRAPHY USING GRAY SCALE VALUES IN DETECTING CARIES

Author

Sankar, Anjali and Raghu Sandhya

Abstract

AIM:The aim of this research was to evaluate the diagnostic accuracy of Cone beam computed tomography(CBCT) using gray scale value in detecting caries. The first objective was to measure the remaining dentin thickness (RDT) using intraoral periapical radiographs, CBCT, sectioning of tooth and compare the same. The second objective was to derive at the grayscale values of normal enamel, normal dentin, affected dentin and infected dentin by comparing the CBCT images with the sectioned tooth. MATERIALS AND METHODS: 10 human permanent premolars and molars with dental caries not involving pulp was collected. The inclusion criterion did not include age, gender, or the reason for extraction. All the teeth were subjected to radiographic evaluation using Radio Visio Graphy (RVG), CBCT and stereomicroscopic evaluation of the sectioned tooth. The remaining dentin thickness was measured by all the three methods. Gray scale value of normal enamel, normal dentin, affected dentin and infected dentin was recorded using CBCT. RESULTS: Statistical analysis using unpaired t-test showed remaining dentin thickness using CBCT and stereomicroscopic analysis to be statistically significant (pCONCLUSION: Based on the gray scale values,CBCT can be considered as an accurate tool for use in the diagnosis of caries.

Published
2022
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28. P193. Right Lateral Amygdala Nucleus Volume in Adolescents and Young Adults With Bipolar Disorder Assessed With High Field Magnetic Resonance Imaging

Author

Ye, Jean, primary, Fan, Siyan, additional, Coman, Daniel, additional, Kolosowska, Natalia, additional, Goldman, Danielle, additional, Spencer, Linda, additional, Qiu, Maolin, additional, Dhaher, Roni, additional, Sankar, Anjali, additional, Colic, Lejla, additional, Mason, Graeme, additional, Rothman, Douglas, additional, Fudge, Julie, additional, Berretta, Sabina, additional, and Blumberg, Hilary, additional

Published
2022
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31. Telehealth Social Rhythm Therapy to Reduce Mood Symptoms and Suicide Risk Among Adolescents and Young Adults With Bipolar Disorder

Author

Sankar, Anjali, primary, Panchal, Priyanka, additional, Goldman, Danielle A., additional, Colic, Lejla, additional, Villa, Luca M., additional, Kim, Jihoon A., additional, Lebowitz, Eli R., additional, Carrubba, Erin, additional, Lecza, Bernadette, additional, Silverman, Wendy K., additional, Swartz, Holly A., additional, and Blumberg, Hilary P., additional

Published
2021
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33. Knowledge, attitude, and practice of ultrasonics in endodontic treatment: A Survey among general practitioners and endodontists.

Author

Arun, Nishitha, Ramesh, Sindhu, and Sankar, Anjali

Subjects
GENERAL practitioners, ENDODONTISTS, ENDODONTICS, ULTRASONICS, DENTAL pulp cavities
Abstract

The use of ultrasonics (US) has greatly expanded in the field of dentistry. Over the past few decades, the application of US has increased substantially in endodontics owing to the predictable prognosis and ease of operation. The objective of this survey was to determine the knowledge, practice, and attitude of US in endodontics among the general practitioners, postgraduates, and endodontists. An electronic questionnaire containing 16 questions regarding the knowledge, attitude, and practice of US in endodontics was circulated among the general dentists, postgraduates, and endodontists and the responses were collected online. Data were statistically examined using IBM SPSS software. A total of 202 dentists (general dentists = 92, endodontists = 77, and postgraduates = 33) participated in the survey. Eighty-nine percent of them were aware of the use of US in endodontics, 36.1% of them preferred using US in the removal of pulp chamber calcifications, pulp stones, access refinement, and troughing hidden canals, and 61.4% chose <3% sodium hypochlorite for root canal irrigation with US. The cost of the ultrasonic unit and heat generation during procedures were considered the greatest limitation in using the US. The majority of the dentists were well aware of the use of US and its advantages in various endodontic procedures but they did not use it routinely in their practice. The use of US has been reported to have greatly increased the predictability of endodontic treatment. [ABSTRACT FROM AUTHOR]

Published
2022
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35. A Graph Theoretical Connectome Measure to Assess Whole Brain Functional Connectivity Disturbances Associated With Suicide Attempts in Bipolar Disorder

Author

Sankar, Anjali, primary, Scheinost, Dustin, additional, Goldman, Danielle, additional, Drachman, Rebecca, additional, Colic, Lejla, additional, Villa, Luca M., additional, Kim, Jihoon A., additional, Gonzalez, Yarani, additional, Marcelo, Imani, additional, Shinomiya, Mei, additional, Pittman, Brian, additional, Lacadie, Cheryl M., additional, Oquendo, Maria, additional, Constable, R. Todd, additional, and Blumberg, Hilary P., additional

Published
2021
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37. Changing gears in the treatment of bipolar disorder through integrated use of electronic devices

Author

Panchal, Priyanka, primary, Kim, Jihoon A., additional, Sankar, Anjali, additional, Goldman, Danielle, additional, Villa, Luca M., additional, Millard, Hun, additional, Carrubba, Erin, additional, Lecza, Bernadette, additional, Merikangas, Kathleen R., additional, Silverman, Wendy K., additional, Swartz, Holly A., additional, and Blumberg, Hilary P., additional

Published
2021
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38. A graph theory‐based whole brain approach to assess mood state differences in adolescents and young adults with bipolar disorder.

Author

Goldman, Danielle A., Sankar, Anjali, Colic, Lejla, Villa, Luca, Kim, Jihoon A., Pittman, Brian, Constable, R. Todd, Scheinost, Dustin, and Blumberg, Hilary P.

Subjects
*YOUNG adults, *BIPOLAR disorder, *FUNCTIONAL magnetic resonance imaging, *CORPUS striatum, *TEENAGERS
Abstract

Objectives: Identifying hubs of brain dysfunction in adolescents and young adults with Bipolar I Disorder (BDAYA) could provide targets for early detection, prevention, and treatment. Previous neuroimaging studies across mood states of BDAYA are scarce and often examined limited brain regions potentially prohibiting detection of other important regions. We used a data‐driven whole‐brain Intrinsic Connectivity Distribution (ICD) approach to investigate dysconnectivity hubs across mood states in BDAYA. Methods: Functional magnetic resonance imaging whole‐brain ICD data were investigated for differences across four groups: BDAYA‐depressed (n = 22), BDAYA‐euthymic (n = 45), BDAYA‐elevated (n = 24), and healthy controls (HC, n = 111). Clusters of ICD differences were assessed for regional dysconnectivity and mood symptom relationships. Analyses were also performed for BDAYA overall (vs. HC) ICD differences persisting across mood states. Results: ICD was higher in the BDAYA‐ depressed group than other groups in bilateral ventral/rostral/dorsal prefrontal cortex (PFC) and right lenticular nucleus (LN) (pcorrected <0.05). In BDAYA‐depressed, functional connectivity (FC) was increased between these regions with their contralateral homologues and PFC‐medial temporal FC was more negative (p < 0.005). PFC‐related findings correlated with depression scores (p < 0.05). The overall BDAYA group showed ICD increases in more ventral left PFC and right cerebellum, present across euthymia and acute mood states. Conclusions: This ICD approach supports a PFC hub of inter‐ and intra‐hemispheric frontotemporal dysconnectivity in BDAYA with potential trait features and disturbances of higher magnitude during depression. Hubs were also revealed in LN and cerebellum, less common foci of BD research. The hubs are potential targets for early interventions to detect, prevent, and treat BD. [ABSTRACT FROM AUTHOR]

Published
2022
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47. Altered frontal cortex functioning in emotion regulation and hopelessness in bipolar disorder.

Author

Sankar, Anjali, Purves, Kirstin, Colic, Lejla, Cox Lippard, Elizabeth T., Millard, Hun, Fan, Siyan, Spencer, Linda, Wang, Fei, Pittman, Brian, Constable, R. Todd, Gross, James J., and Blumberg, Hilary P.

Subjects
*EMOTION regulation, *BIPOLAR disorder, *SUICIDE risk factors, *SUICIDAL behavior, *DESPAIR, *EMOTIONS
Abstract

Objectives: Emotion regulation difficulties precipitate and exacerbate acute mood symptoms in individuals with bipolar disorder (BD), and contribute to suicidal behavior. However, few studies have examined regional brain responses in explicit emotion regulation during acute BD mood states, or hopelessness, a major suicide risk factor. We assessed brain responses during explicit emotion regulation, and their relationship with hopelessness, in acutely symptomatic and euthymic individuals with BD. Methods: Functional MRI data were obtained from individuals with BD who were either in acute negative (BD‐A; n = 24) or euthymic (BD‐E; n = 24) mood states, and from healthy volunteers (HV; n = 55), while participants performed a paradigm that instructed them to downregulate their responses to fearful (EmReg‐Fear) and happy (EmReg‐Happy) facial stimuli. Emotion regulation‐related differences in brain responses during negative and euthymic BD states, as well as their associations with negative affective symptoms (hopelessness and depression), were examined. Results: Decreased responses were observed in ventral and dorsal frontal regions, including medial orbitofrontal (mOFC) and dorsal anterior cingulate cortices, during EmReg‐Fear across symptomatic and euthymic states in participants with BD relative to HVs. The lowest responses were observed in the BD‐A group. Across BD participants, negative associations were observed between mOFC responses and hopelessness, particularly due to loss of motivation. Differences were not significant during EmReg‐Happy. Conclusions: Lesser emotion regulation‐related ventral and dorsal frontal engagement in BD could represent a trait abnormality that worsens during acute negative states. The reduced mOFC engagement in BD during explicit regulation of negative emotions may contribute to hopelessness particularly in the context of diminished motivation. [ABSTRACT FROM AUTHOR]

Published
2021
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