Function In Major Depressive Disorder Research Articles

Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis

BackgroundFunctional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples. MethodsWe conducted a meta-analysis of studies reporting changes in brain activity (e.g., as indexed by positron emission tomography) following treatments with selective serotonin reuptake inhibitors (SSRIs), electroconvulsive therapy (ECT), or transcranial magnetic stimulation. Additionally, we examined the statistical reliability of overlap among thresholded meta-analytic SSRI, ECT, and transcranial magnetic stimulation maps as well as a map of abnormal neural function in MDD. ResultsOur meta-analysis revealed that 1) SSRIs decrease activity in the anterior insula, 2) ECT decreases activity in central nodes of the default mode network, 3) transcranial magnetic stimulation does not result in reliable neural changes, and 4) regional effects of these modes of treatment do not significantly overlap with each other or with regions showing reliable functional abnormality in MDD. ConclusionsSSRIs and ECT produce neurally distinct effects relative to each other and to the functional abnormalities implicated in depression. These treatments therefore may exert antidepressant effects by diminishing neural functions not implicated in depression but that nonetheless impact mood. We discuss how the distinct neural changes resulting from SSRIs and ECT can account for both treatment effects and side effects from these therapies as well as how to individualize these treatments.

Assessing and measuring cognitive function in major depressive disorder

Cognitive dysfunction is a major component of major depressive disorder (MDD). No ‘gold-standard’ tool exists for the assessment of cognitive dysfunction for adults with MDD. The use of measurement-based care...

Brain mechanisms of anxiety's effects on cognitive control in major depressive disorder.

Adults with major depressive disorder (MDD) demonstrate increased susceptibility to interfering effects of anxiety on cognitive control; although under certain conditions adults with MDD are able to compensate for these effects. The brain mechanisms that may facilitate the ability to compensate for anxiety either via the recruitment of additional cognitive resources or via the regulation of interference from anxiety remain largely unknown. To clarify these mechanisms, we examined the effects of anxiety on brain activity and amygdala-prefrontal functional connectivity in adults diagnosed with MDD. A total of 22 unmedicated adults with MDD and 18 healthy controls (HCs) performed the Tower of London task under conditions designed to induce anxiety, while undergoing a functional magnetic resonance imaging assessment. During the easy condition, the MDD group demonstrated equivalent planning accuracy, longer planning times, elevated amygdala activity and left rostrolateral prefrontal cortex (RLPFC) hyperactivity relative to HCs. Anxiety mediated observed group differences in planning times, as well as differences in amygdala activation, which subsequently mediated observed differences in RLPFC activation. During the easy condition, the MDD group also demonstrated increased negative amygdala-dorsolateral prefrontal cortex (DLPFC) connectivity which correlated with improved planning accuracy. During the hard condition, HCs demonstrated greater DLPFC activation and stronger negative amygdala-DLPFC connectivity, which was unrelated to planning accuracy. Our results suggest that persons with MDD compensate for anxiety-related limbic activation during low-load cognitive tasks by recruiting additional RLPFC activation and through increased inhibitory amygdala-DLPFC communication. Targeting these neural mechanisms directly may improve cognitive functioning in MDD.

Patient-reported functioning in major depressive disorder.

Compared with the general population, patients with major depressive disorder (MDD) report substantial deficits in their functioning that often go beyond the clinical resolution of depressive symptoms. This study examines the impact of MDD and its treatment on functioning. From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult outpatients with MDD at entry and exit points of each level of antidepressant treatment and again 12 months post treatment. Functioning was measured using the Work and Social Adjustment Scale (WSAS). The results show that only 7% of patients with MDD reported within-normal functioning before treatment. The proportion of patients achieving within-normal functioning (WSAS) scores significantly increased after treatment. However, the majority of patients (>60%) were still in the abnormal range on functioning at exit. Although remitted patients had greater improvements compared with nonremitters, a moderate proportion of remitted patients continued to experience ongoing deficits in functioning after treatment (20-40%). Follow-up data show that the proportions of patients experiencing normal scores for functioning after 12 months significantly decreased from the end of treatment to the follow-up phase, from 60.1% to 49% (p < 0.0001), a finding that was particularly significant in nonremitters. Limitations of this study include the reliance on self-report of functioning and the lack of information on patients who dropped out. This study points to the importance of functional outcomes of MDD treatment as well as the need to develop personalized interventions to improve functioning in MDD.

Neurocognitive Changes in Selective Serotonin Reuptake Inhibitors—Treated Adolescents with Depression

Adolescents with major depressive disorder (MDD) were found to have deficits in executive function, attention, and memory. Despite the fact that some neurocognitive functions have been shown to be present in acute stage of the illness, but not in remission, longitudinal studies are lacking. The current study aimed to investigate the changes in neurocognitive functioning in adolescents with depression during an acute treatment course with selective serotonin reuptake inhibitor. Twenty-four adolescents with current MDD and 24 healthy controls (HCs) were administered subtests of the Cambridge Neuropsychological Test Automated Battery as well as clinical scales at baseline and were retested at weeks 6 and 12. Those with MDD were started on fluoxetine after the baseline assessment. Despite considerable improvement in depressive symptoms in the MDD group, there was a persistent deficit in visual memory in the MDD group over time compared with HCs (p = 0.001). On a task of sustained attention and inhibition, HCs became better at detecting target sequences at week 12 while there were residual sustained attention deficits in MDD (p = 0.01). On an executive function (planning) task, while HCs learned the task and improved substantially in performance over 12 weeks, MDD performance did not significantly change (p = 0.04). When treating depressed adolescents, clinicians need to also monitor cognitive symptoms as they appear to lag behind mood symptoms in improvement.

Monitoring of liver function in major depressive disorder treated with SSRI

BackgroundMajor depressive disorder is one of the most prevalent psychiatric illnesses in the world affecting more than 12% of men and more than 21% of women in their lifetime. Selective serotonin reuptake inhibitors (SSRIs) are worldwide prescribed to treat depression. SSRIs drugs can cause drug-induced liver injury (DILI).AimsThe aim of the study was to evaluate the liver function in patients treated with SSRI in order to detect DILI.MethodsAll the patients with first major depressive episode treated with the same SSRI antidepressant for at least 3 months between September 2013 and September 2015 were entered into the study. The hepatic function panel included aminotransferases, total and direct bilirubin, albumin, total protein, gamma glutamyl transferase (GGT), LDH cholesterol, hepatitis B virus (HBV), and hepatitis C virus (HCV).ResultsOf 134 subjects with MDD according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who met inclusion criteria, 98 patients entered into study. Seventy-seven (76.5%) were treated with SSRI for at least 3 months with mean age were 45.4 (SD = 6.3), 65 women (66.3%). Five patients (5.1%) were newly diagnosed with hepatitis, and 10 (10.2%) presented elevated values of ALT, AST. The mean duration of depressive symptoms was 9.2 months (SD = 6.9).ConclusionsThe treatment with SSRI seems to be effective and safe in our sample. A relative small number of patients with MDD were diagnosed with viral hepatitis during this cross-sectional study. Further randomized and controlled trials are needed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

ID 515 – Mood dysregulation, sex and sex hormones predict stress response circuitry deficits

Inspired by the NIMH RDoC initiative to determine biosignatures associated with regulation of arousal and negative affect across psychiatric disorders, we used a mild visual stress task to conduct a functional magnetic resonance imaging (fMRI) study investigating the impact of depressed mood on stress circuitry function in major depressive disorder, psychosis and healthy controls ( n = 99). fMRI data were analyzed using SPM8 and task-related connectivity was assessed by generalized psychophysiological interaction (gPPI). Hyperactivity in subcortical arousal regions in response to stress was shared across diagnoses. Sex-specific analyses revealed that in females but not males depressed mood predicted increase in R AMYG response and decrease in (1) R AMYG–R HIPP, (2) R AMYG-R OFC, and (3) HYPO–R OFC connectivity during stress. Follow-up analyses showed that the positive relationship between depressed mood and stress-related increase in R AMYG–R HIPP connectivity was present in males with high but not low free androgens. Overall, these findings demonstrated that females with depressed mood were unable to recruit regions inhibiting subcortical arousal during stress, possibly explaining why women are more vulnerable to mood disorders than men, and that testosterone might have protective effects on stress circuitry function in men.

Cognition in major depressive disorder: a 'Systemically Important Functional Index' (SIFI).

Cognitive dysfunction in major depressive disorder (MDD) is common, pervasive across multiple subdomains of cognitive function, and is a principle determinant of health outcomes from patient, provider, and societal perspectives. The overarching aim herein is to provide rationale for the evaluation, measurement, and specific treatment of cognitive function in adults with MDD. Evidence indicates that cognitive dysfunction in MDD is a critical mediator of workplace disability. Systematic evaluation and measurement of cognitive function is warranted. All individuals with MDD should be evaluated for both objective and subjective cognitive dysfunction. Although differences between antidepressants in overall antidepressant efficacy are not consistent, unequivocal differences in improving measures of cognitive function are noted with evidence indicating that vortioxetine has multidomain cognitive benefits, whereas duloxetine has replicated evidence of improving measures of acquisition and recall (i.e. memory). The probability of functional recovery in MDD is likely to increase with interventions that specifically target and improve measures of cognitive function. Clinicians are encouraged to evaluate patients using a validated measure (e.g. the THINC-it tool); prevention of cognitive impairment in MDD is a critical therapeutic priority. Vortioxetine and duloxetine benefit measures of cognitive function in MDD. Preliminary evidence of beneficial effects on cognitive emotional processing are reported with ketamine.

Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project.

Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.

Treating to target in major depressive disorder: response to remission to functional recovery.

Treating to target in chronic diseases [e.g. Major Depressive Disorder (MDD)] fosters precision, consistency, and appropriateness of treatment selection and sequencing. Therapeutic target definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations. Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives. Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health. Several atypical antipsychotic agents (i.e. brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD. Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD. Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery. Measurement-based care, health information technology/systems, and integrated care models (e.g. medical homes) provide requisite tools and health environments for optimal health outcomes in MDD. Achieving remission in MDD does not equate to health. Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (i.e. optimization of human capital). As in other chronic diseases, treating to target (e.g. cognitive function) further increases the probability of achieving optimal health outcomes.

Altered functional interaction hub between affective network and cognitive control network in patients with major depressive disorder

Emotional and cognitive dysregulation in major depressive disorder (MDD) have been consistently considered to be attributed to structural and functional abnormalities in affective network (AN) and cognitive control network (CCN). This study was to investigate the functional connectivity (FC) patterns and altered functional interactions between both networks in MDD. We investigated resting-state functional connectivity magnetic resonance imaging in the AN and the CCN in 25 MDD and 35 healthy controls (HC). The seeds were from voxel-based morphometry (VBM) analysis results. Then FC within the AN was assessed from a seed placed in the left amygdala (AMG) and FC within CCN was determined by placing seeds in the right dorsolateral prefrontal cortex (DLPFC). Compared with HC, MDD showed reduced FC between left AMG and bilateral precuneus and right anterior cingulated cortex (ACC) within AN and reduced FC between right DLPFC and left cuneus, left lingual gyrus, and right ACC within CCN. An interaction hub of altered FC in MDD between AN and CCN located in the right ACC. Interestingly, the altered FC between right ACC and left AMG was negatively correlated with depressive symptom score while the altered FC between right ACC and DLPFC was positively correlated the executive function in MDD. The right ACC not only supports the cognitive and emotional processes, but also is an altered functional interaction hub between AN and CCN in MDD. It further suggest multiple sources of dysregulation in AN and CCN implicate both top-down cognitive control and bottom-up emotional expression dysfunction in MDD.

Evidence for alterations of the glial syncytial function in major depressive disorder

BackgroundGlial cells are essential in maintaining synaptic function. In glutamatergic synapses astrocytes remove the products of neural activity, (i.e. potassium, glutamate and excess water) from the synaptic cleft and redistribute them across the glial network; these products of neural activity can then be recycled for neuronal use or released into the vascular compartment. This type of highly coupled cell network -or syncytium-maintains the balance of synaptic activity by restoring the basal levels of such molecules in the synaptic cleft. Previous studies have reported alterations of glia related genes in Major Depressive Disorder, including some genes related to syncytial function. MethodsWe used RNA isolated from hippocampal tissues of 13 MDD subjects and 10 healthy controls to broadly examine gene expression using microarrays. Hippocampal RNA samples were isolated by laser capture microdissection from human tissue sections carefully avoiding contamination from neighboring structures. Once RNA quality was validated RNA was labeled and hybridized to microarrays. ResultsAnalysis of microarray data identified mRNA transcripts involved in glial syncytial function that were downregulated in MDD subjects compared to controls, including potassium and water channels (KCNJ10, AQP4), gap junction proteins (GJA1) and glutamate transporters (SLC1A2, SLC1A3). These gene expression differences were confirmed by qPCR. ConclusionsThe downregulation of these genes related to the syncytial network activity of glial cells is consistent with the hypothesis that synaptic homeostasis is disrupted thereby disrupting hippocampal synaptic function in MDD patients. Such glial gene expression changes could contribute either to the onset or perpetuation of depressive symptoms and hence, represent targets for novel therapeutics.

V22. EEG-vigilance and the autonomous nervous system in the prediction of antidepressant treatment: Findings from the iSPOT-D study

To overcome the limitations of the syndrome-based diagnostic routine in neuropsychiatric disorder and to provide biomarker-informed decisions for treatment, recently the Research Domain Criteria have been initialized[1]. They include separate criteria for autonomous and arousal systems. Based on findings of altered wakefulness-regulation and autonomous function in major depressive disorder (MDD), the goal of this study therefore was to investigate the predictive value for treatment outcome of central nervous system (CNS) and autonomous nervous system (ANS) arousal and their interaction in a large cohort of patients from the iSPOT-D trial that received either a selective-serotonin reuptake-inhibitor (SSRI) or a serotonin-norepinephrine-reuptake-inhibitor (SNRI). Methods CNS and ANS-arousal (defined by electroencephalogram vigilance and heart rate) and their change over time were assessed during rest. Differences of treatment outcome as defined by the decline of Hamilton Rating Scale for Depression-(HRSD) from baseline to week 8 after treatment initiation for the whole sample and for SSRI and SNRI groups separately were analysed using a binary logistic regression model and repeated measure analysis of variance (ANOVA). Results Responders and remitters were characterized by a steeper decline of CNS-arousal. Subgroup analysis showed that this effect was only present for the SSRI arm whereas SNRI responders showed a more pronounced increase of ANS-arousal. Further, SSRI responders showed a correlation between ANS and CNS measures, SSRI non-responders and the whole SNRI subgroup did not. Conclusions CNS and ANS-arousal during rest predict positive treatment outcome to antidepressant medication. The differences of CNS and ANS-profiles for SSRI or SNRI prediction are interpreted as neurophysiological traits that indicate responsiveness to different drug-classes rather than disorder specific aspects.

A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder.

This multicenter, randomized, double-blind, placebo-controlled, active-referenced (duloxetine 60 mg), parallel-group study evaluated the short-term efficacy and safety of vortioxetine (10–20 mg) on cognitive function in adults (aged 18–65 years) diagnosed with major depressive disorder (MDD) who self-reported cognitive dysfunction. Efficacy was evaluated using ANCOVA for the change from baseline to week 8 in the digit symbol substitution test (DSST)–number of correct symbols as the prespecified primary end point. The patient-reported perceived deficits questionnaire (PDQ) and physician-assessed clinical global impression (CGI) were analyzed in a prespecified hierarchical testing sequence as key secondary end points. Additional predefined end points included the objective performance-based University of San Diego performance-based skills assessment (UPSA) (ANCOVA) to measure functionality, MADRS (MMRM) to assess efficacy in depression, and a prespecified multiple regression analysis (path analysis) to calculate direct vs indirect effects of vortioxetine on cognitive function. Safety and tolerability were assessed at all visits. Vortioxetine was statistically superior to placebo on the DSST (P<0.05), PDQ (P<0.01), CGI-I (P<0.001), MADRS (P<0.05), and UPSA (P<0.001). Path analysis indicated that vortioxetine's cognitive benefit was primarily a direct treatment effect rather than due to alleviation of depressive symptoms. Duloxetine was not significantly different from placebo on the DSST or UPSA, but was superior to placebo on the PDQ, CGI-I, and MADRS. Common adverse events (incidence ⩾5%) for vortioxetine were nausea, headache, and diarrhea. In this study of MDD adults who self-reported cognitive dysfunction, vortioxetine significantly improved cognitive function, depression, and functionality and was generally well tolerated.

Cognitive dysfunction in depression - pathophysiology and novel targets.

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Molecular and Genetic Characterization of Depression: Overlap with Other Psychiatric Disorders and Aging

Genome-wide expression and genotyping technologies have uncovered the genetic bases of complex diseases at unprecedented rates. However, despite its heavy burden and high prevalence, the molecular characterization of major depressive disorder (MDD) has lagged behind. Transcriptome studies report multiple brain disturbances but are limited by small sample sizes. Genome-wide association studies (GWAS) report weak results but suggest an overlapping genetic risk with other neuropsychiatric disorders. We performed a systematic molecular characterization of altered brain function in MDD using meta-analysis of differential expression of 8 gene array studies across 3 corticolimbic brain regions in 101 subjects. The identified ‘metaA-MDD' genes suggest altered neurotrophic support, brain plasticity and neuronal signaling in MDD. Notably, metaA-MDD genes display a low connectivity and hubness in coexpression networks as well as a uniform genomic distribution, which is consistent with diffuse polygenic mechanisms. We have integrated these findings with results from over 1,800 published GWAS and show that genetic variations nearby metaA-MDD genes predict a greater risk for neuropsychiatric disorders, and notably for age-related phenotypes, but not for other medical illnesses (including those frequently co-occurring with depression) or body characteristics. Collectively, the intersection of unbiased investigations of gene function (transcriptome) and structure (GWAS) provides novel leads to investigate molecular mechanisms of MDD and suggests common biological pathways between depression, other neuropsychiatric diseases and brain aging.

The relationship between neurocognitive and psychosocial functioning in major depressive disorder: a systematic review.

Neurocognitive deficits are demonstrated in major depressive disorder (MDD) and most likely contribute to the functional impairment experienced by affected individuals. We systematically reviewed the evidence on neurocognitive deficits and their relationship(s) to psychosocial functioning in MDD. English-language literature was searched in MEDLINE, EMBASE, Science Direct, and PsycInfo databases for the years 1980-October 15, 2013, with the following terms: (depressive disorder or depressive disorder, major) and permutations of (cognitive, neurocognitive, neuropsych*) with (impairment, deficit, performance, test) and (quality of life; functional outcomes; outcome assessment, health care) or (assessment, outcomes; assessment, patient outcomes; outcomes assessment; outcomes assessments, patient). Inclusion criteria were (1) nongeriatric adults (< 60 years) with a primary diagnosis of MDD by DSM-IV, ICD-9, or ICD-10 criteria; (2) use of neuropsychological tests; and (3) use of a specific measure of social, occupational, or daily functioning. Of 488 articles identified in the initial search, 10 met the inclusion criteria. Two independent appraisers assessed eligibility of the studies. Substantial heterogeneity in the samples and methods precluded a quantitative meta-analysis, so we performed a narrative descriptive review. The included studies employed a variety of neurocognitive tests and assessments of psychosocial functioning. Overall, depressed samples had neurocognitive deficits in various domains that were associated with different measures of psychosocial functioning. However, these findings were constrained by methodological limitations of studies. The limited evidence base suggests that neurocognitive functioning appears to be broadly associated with functional impairment in individuals with MDD, but the quality of evidence is weak. Further studies to clarify the relationship(s) between neurocognitive and psychosocial functioning in MDD will benefit from larger and more homogeneous samples, prospective designs with multivariate analyses, and use of comprehensive assessments of psychosocial functioning that are validated in depressed populations.

Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: A tract-specific analysis study

BackgroundThe corpus callosum modulates interhemispheric communication and cognitive processes. It has been suggested that white matter abnormalities in the corpus callosum are related to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to examine microstructural abnormalities in callosal fibers separated by their connection to functional brain regions and determine the relationship of these abnormalities with cognitive function in MDD and BD. MethodsThe subjects were 18 patients with MDD, 20 patients with BD, and 21 healthy controls. The callosal fibers were divided into 6 segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. We examined differences in the fractional anisotropy (FA) of callosal fibers in six segments among the three subject groups and examined the correlation between the FA in each segment and cognitive performance in the 3 groups. ResultsThe FA of anterior callosal fibers were reduced significantly in the MDD and BD groups compared to those in the HC group, and the FA of anterior callosal fibers correlated significantly with the raw scores of the digit sequencing task and symbol coding in the MDD group. LimitationsThe patients were medicated at the time of scanning, and the MDD and BD groups were not matched for symptom severity. ConclusionsOur results suggest that MDD and BD have similar microstructural abnormalities in anterior callosal fibers connecting bilateral frontal cortices, and these abnormalities may be related to impairment of working memory and attention in MDD.

Dentate gyrus volume and memory performance in major depressive disorder

BackgroundMagnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Patients with MDD have consistently demonstrated worse performance than healthy controls a number of memory tests. Memory functions within the hippocampus in healthy younger subjects appear to be linked to cornu ammonis (CA1-3) and dentate gyrus (DG) subfields. Therefore, the main goal of the present study was to investigate whether memory deficits in MDD patients are related to reduction in hippocampal subfields volumes, particularly DG and CA 1–3. Methods15 MDD patients meeting DSM-IV criteria for MDD with moderate or severe episodes were recruited, together with 15 healthy controls. We used T2-weighted 2D Fast Spin Echo (FSE) and T1-weighted 3D MPRAGE sequences at 4.7T to compare hippocampal subfield volumes at 0.09μl voxel volume. Participants were administered the Wechsler Memory Scale. ResultsMDD patients underperformed in several episodic visual memory tasks, as well as in visual working memory, compared to healthy controls. Global hippocampal volumes were similar between groups; however, MDD patients showed significantly reduced DG volumes within the hippocampal body. Duration of depression correlated with MDD patients׳ total volumes in the hippocampal body and CA1-3 and DG subfields within it. LimitationsOur study sample was relatively small and the majority of patients were on antidepressant treatment. ConclusionsOur findings suggest that DG volumes in particular may be worthy of further study to further elucidate their precise role in MDD, both by itself as well as in relation to memory.

P.2.b.030 Interaction between depression remission status and salivary cortisol in relation to cognitive function in major depressive disorder

P.2.b.030 Interaction between depression remission status and salivary cortisol in relation to cognitive function in major depressive disorder