A systematic review and meta-analysis of the neural correlates of psychological therapies in major depression

Longitudinal neuroimaging studies in major depression have revealed cortico-limbic abnormalities which are modulated by treatment. We performed a systematic review and metaanalysis of psychotherapy treatment studies measuring neural function and metabolism using fMRI, PET, SPECT and MRS. Seventeen studies were included in the systematic review, total of 200 major depression participants (mean age 37.6 years), all medication free, and 116 healthy controls (mean age 36.4 years). Neuroimaging assessments were performed prior to initiation of treatment and following course of treatment. Treatment durations were: 16-30 weeks for CBT, 11 weeks for behavioral activation therapy, and up to 15 months for psychodynamic psychotherapy. The meta-analysis consisted of studies in which both groups had same serial scans and comparable tasks; total of 5 studies with visual presentation tasks of emotional stimuli: 55 patients (mean age: 38.7 years) and 55 healthy controls (mean age: 36.3 years). The meta-analysis revealed a significant group by time effect in left rostral anterior cingulate, in which patients showed increased activity following psychotherapy while healthy controls showed a decrease at follow up. Longitudinal treatment effects revealed reduced left precentral cortical activity in major depression. Findings could be indicative of improvements in emotion responsivity that may be achieved following psychotherapy

Diagnostic potential of structural neuroimaging for depression from a multi-ethnic community sample

Background At present, we do not have any biological tests which can contribute towards a diagnosis of depression. Neuroimaging measures have shown some potential as biomarkers for diagnosis. However, participants have generally been from the same ethnic background while the applicability of a biomarker would require replication in individuals of diverse ethnicities. Aims We sought to examine the diagnostic potential of the structural neuroanatomy of depression in a sample of a wide ethnic diversity. Method Structural magnetic resonance imaging (MRI) scans were obtained from 23 patients with major depressive disorder in an acute depressive episode (mean age: 39.8 years) and 20 matched healthy volunteers (mean age: 38.8 years). Participants were of Asian, African and Caucasian ethnicity recruited from the general community. Results 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%. A widespread network encompassing frontal, parietal, occipital and cerebellar regions contributed towards diagnostic classification. Conclusions These findings provide an important step in the development of potential neuroimaging-based tools for diagnosis as they demonstrate that the identification of depression is feasible within a multi-ethnic group from the community. Declaration of interests C.H.Y.F. has held recent research grants from Eli Lilly and Company and GlaxoSmithKline. L.M. is a former employee and stockholder of Eli Lilly and Company

Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine

Background: Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. Methods: Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI. Results: A significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response. Conclusions: Baseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation. Trial registration: Registered at clinicaltrials.gov (NCT01051466)

Other race effect on amygdala response during affective facial processing in major depression

Objective: The other race effect, also known as own race bias, refers to the enhanced ability to recognize faces belonging to one’s own race relative to faces from another race. The other race effect is associated with increased amygdala response in healthy individuals. The amygdala is a key node in emotion processing which shows impaired functioning in depression and has been proposed to be a marker of depressive state. We investigated the impact of the other race effect on amygdala responses in depression. Methods: Participants were 30 individuals with major depression (mean age39.4 years) and 23 healthy individuals (mean age: 38.8 years) recruited from the community. Participants were Asian, Black/African American and Caucasian. During a functional MRI scan, participants viewed Caucasian faces which displayed a range of sad expressions. A region of interest analysis of left and right amygdala responses was performed. Results: Increased bilateral amygdala responses were observed in response to the Caucasian face stimuli in participants who were Asian or Black/African American as compared to Caucasian participants in both healthy individuals and individuals with major depression. There was no significant group by race interaction effect. Conclusions: Increased amygdala responses associated with the other race effect were evident in both individuals with major depression and in healthy participants. Increased amygdala responses with the other race effect is a potential confound of the neural correlates of facial processing in healthy participants and in mental health disorders. The implications of the other race effect on impairments in interpersonal functioning in depression require further investigation

Association of SUMOlation Pathway Genes With Stroke in a Genome-wide Association Study in India

OBJECTIVE: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population. METHODS: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked. RESULTS: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker–based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10(−8). The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus (p(lowest) = 1.74 × 10(−58)) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10(−9)) and 18-carbon fatty acid metabolism (p = 7.36 × 10(−12)). In gene-based analysis, we identified 3 genes (SLC17A2, FAM73A, and OR52L1) at p < 2.7 × 10(−6). Eleven of 32 candidate gene loci studied in an Indian population replicated (p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect. CONCLUSIONS: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke

Recent Advances in Neuroimaging of Mood Disorders: Structural and Functional Neural Correlates of Depression, Changes with Therapy, and Potential for Clinical Biomarkers

Opinion Statement: Major depressive disorder (MDD) is associated with key regions of the brain involved in emotional processing. The present meta-analysis revealed widespread structural reductions in limbic and prefrontal regions that occur in MDD, with no regions of increased grey matter volume. Functional impairments involve many of the same regions with dysregulated interactions between limbic and cortical structures. Longitudinal treatment studies have predominantly investigated pharmacological therapies, and there have been fewer studies of psychological treatments. Reports of increased hippocampal volume and reductions in amygdala activation following treatment suggest implications for the course of illness and the impact of pharmacological as well as psychological therapies. Measures of regional brain volume and activity during an acute depressive episode prior to or early in the course of treatment offer the potential to develop predictors of clinical response. High predictive accuracy at the level of the individual is essential for translation of these findings to clinical use. Development of such biomarkers may help to guide treatment strategies, particularly for individuals who may not benefit from current first-line therapeutic options, in order to preclude a potential series of ineffective treatment trials

Effects of antidepressant therapy on neural components of verbal working memory in depression

Impairments in verbal working memory are evident in major depression. Verbal working memory is comprised of the components of encoding, maintenance and retrieval. Whether the neural impairments are expressed in specific components, and how pharmacological therapy could modify the neural correlates are not well understood. We investigated the neural correlates of verbal working memory components in depression using the Sternberg task in a longitudinal magnetic resonance imaging study. Serial scans were acquired in 23 patients (mean age 39.8 years) during an acute depressive episode and following 12 weeks of pharmacological therapy with duloxetine and in 22 matched healthy controls (mean age 39.1 years) at the same time points. A significant group by time interaction was evident during the long maintenance phase, extending from the left middle frontal to the middle temporal and caudate regions, in which there was reduced activation in healthy participants at the follow -up scan but there were no changes in patients. Persistent neural engagement during the maintenance phase following treatment was revealed in major depression. The findings emphasize that impairments in verbal working memory may be initiated in the maintenance phase in major depression in order to sustain performance. Further research with larger sample size and using randomized, placebo-controlled double-blind studies are required to confirm our results