Clinical Features Of Major Depressive Disorder Research Articles

EEG-based major depressive disorder recognition by neural oscillation and asymmetry.

Major Depressive Disorder (MDD) is a pervasive mental health issue with significant diagnostic challenges. Electroencephalography (EEG) offers a non-invasive window into the neural dynamics associated with MDD, yet the diagnostic efficacy is contingent upon the appropriate selection of EEG features and brain regions. In this study, resting-state EEG signals from both eyes-closed and eyes-open conditions were analyzed. We examined band power across various brain regions, assessed the asymmetry of band power between the hemispheres, and integrated these features with clinical characteristics of MDD into a diagnostic regression model. Regression analysis found significant predictors of MDD to be beta2 (16-24 Hz) power in the Prefrontal Cortex (PFC) with eyes open (B = 20.092, p = 0.011), beta3 (24-40 Hz) power in the Medial Occipital Cortex (MOC) (B = -12.050, p < 0.001), and beta2 power in the Right Medial Frontal Cortex (RMFC) with eyes closed (B = 24.227, p < 0.001). Asymmetries in beta1 (12-16 Hz) power with eyes open (B = 28.047, p = 0.018), and in alpha (8-12 Hz, B = 9.004, p = 0.013) and theta (4-8 Hz, B = -13.582, p = 0.008) with eyes closed were also significant predictors. The study confirms the potential of multi-region EEG analysis in improving the diagnostic precision for MDD. By including both neurophysiological and clinical data, we present a more robust approach to understanding and identifying this complex disorder. The research is limited by the sample size and the inherent variability in EEG signal interpretation. Future studies with larger cohorts and advanced analytical techniques are warranted to validate and refine these findings.

Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis.

Major depressive disorder (MDD) is associated with significant cognitive deficits during the acute and remitted stages. The aim of this systematic review and meta-analysis was to examine the course of cognitive function whilst considering demographic, treatment, or clinical features of MDD that could moderate the extent of cognitive change. Databases were searched to identify studies that reported on cognitive function in MDD with a ≥12-week test-retest interval. Relevant studies were pooled using random effects modelling to generate an inverse-variance, weighted, mean effect size estimate (Hedges' g) of cognitive change for each cognitive variable and for an overall composite cognitive domain. Of 6898 records, 99 eligible studies were identified from which 69 were meta-analysed, consisting of 4639 MDD patients (agemean = 40.25years, female% = 64.62%) across 44 cognitive variables. In over 95% of cognitive variables, improvements were either of non-significant, negligible, or of a small magnitude, and when compared to matched healthy controls, the possibility of practice effects could not be precluded. Depressive symptom improvement and the number of previous depressive episodes moderated the extent of cognitive change, demonstrating state- and scar-like features for one-quarter of the cognitive domains. Further longitudinal studies are required to elucidate the MDD cognitive trajectory from initial onset. Findings nonetheless suggest that following pharmacological and non-pharmacological treatment, cognitive change in MDD is typically small, but the capacity for change may be less with episode recurrence. Targeting cognition early in the course of illness may facilitate better prognosis and support a more complete functional recovery.

Decreased cortical gyrification in major depressive disorder.

Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD. We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan-Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group. Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen's f2 = 0.361; p = 1.78 × 10-13). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups. These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.

Regionally decreased cortical gyrification in patients with major depressive disorder

IntroductionEarly neurodevelopmental deviations, such as abnormal cortical folding patterns, are a candidate biomarker for major depressive disorder (MDD). Previous studies on patterns of abnormal cortical gyrification in MDD have provided valuable insights; however, the findings on cortical folding are controversial.ObjectivesWe aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level and the association of the LGI with clinical characteristics of MDD, including recurrence, remission status, illness duration, severity of depression, and medication status of patients with MDD.MethodsWe obtained T1-weighted images of 234 patients with MDD and 215 healthy controls (HCs). LGI values were automatically calculated using the FreeSurfer software according to the Desikan–Killiany atlas. LGI values from 66 cortical regions in the bilateral hemispheres were analyzed. We compared the LGI values between the MDD and HC groups using the analysis of covariance, including patients’ age, sex, and years of education as covariates. The association between clinical characteristics and LGI values was investigated in the MDD group.ResultsCompared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the highest effect size in the left pars triangularis (Cohen’s f = 0.361; P = 1.78 × 10-13). As for the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration of MDD were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between MDD and HC groups.ConclusionsConsidering that the aforementioned cortical regions are involved in emotion regulation, abnormal cortical folding patterns in such regions may be associated with the dysfunction of emotion regulation-related neural circuits, which may lead to MDD. These findings suggest that LGI may be a relatively stable neuroimaging marker associated with the trait of MDD predisposition.Disclosure of InterestNone Declared

Migraine associated with early onset postpartum depression in women with major depressive disorder

Major depressive disorder (MDD) and migraine are both more common among women than men. Women’s reproductive years are associated with increased susceptibility to recurrence of both conditions, suggesting a potential role of sex hormones in aetiology. We examined associations between comorbid migraine and clinical features of MDD in women, including relationships with lifetime reproductive events such as childbirth. Lifetime clinical characteristics and reproductive events in a well-characterised sample of 222 UK women with recurrent MDD, with (n = 98) and without (n = 124) migraine were compared. Women had all been recruited as part of a UK-based ongoing programme of research into the genetic and non-genetic determinants of mood disorders. Multivariate analysis showed a specific association between the lifetime presence of migraine and postpartum depression (PPD) within 6 weeks of delivery (OR = 2.555; 95% CI: 1.037–6.295, p = 0.041). This association did not extend to a broader definition of PPD with onset up to 6 months postpartum. All other factors included in the analysis were not significantly associated with the presence of migraine: family history of depression, younger age at depression onset, history of suicide attempt and severe premenstrual syndrome symptoms. The finding that women with MDD and comorbid migraine may be particularly sensitive to hormonal changes early in the postpartum period leads to aetiological hypotheses and suggests this group may be useful for future studies attempting to characterise PPD and MDD phenotypes. The refinement of such phenotypes has implications for individualising risk and treatment and for future biological and genetic studies.

Psychosocial functionality in depressive workers: A study on associated factors.

Major Depressive Disorder (MDD) has been shown a high prevalence and debilitating mental health. Most of the burden comes from reduced work functioning and frequent or long-term absenteeism. Describe psychosocial functionality in sample of workers with MDD and observe associated factors with sick-leave. Cross-sectional study. Participants were 172 formal workers with MDD according to Mini International Neuropsychiatric Interview. They were classified as active (n = 76) or in sick leave (n = 96). Functionality Assessment Short Test (FAST) was used and the variables were: personal, clinical, and occupational characteristics. Descriptive, bivariate and hierarchical multivariate analyses were conducted; significant with p < .05. Most of the sample was female and <50. Workers in sick leave were older, less physically active, and presented worse scores in global and in each domain of functionality (FAST). High autonomy at working process, perceived stressing work, do not enjoy the work and low resilience to work adversities were significantly associated with sick leave (p < .05). Regarding clinical characteristics of MDD, severity, clinical comorbidity and recidivate subtype were associated with sick leave outcome (p < .05). Sick leave is an important indicator of global functionality. Effective strategies to reduce MDD burden ought to involve some perspectives: (1) Diagnosis and efficient treatment; (2) Promotion and monitoring of functionality and rehabilitation programs; (3) Subject-centered actions that help workers cope with adversities, mitigate stress, and increase satisfaction at work.

43 - GENOME-WIDE ASSOCIATION ANALYSES IDENTIFY 44 RISK VARIANTS AND REFINE THE GENETIC ARCHITECTURE OF MAJOR DEPRESSIVE DISORDER

Background Major Depressive Disorder (MDD) is a notably complex illness with a lifetime prevalence of 14%. It is often chronic or recurrent and is thus accompanied by considerable morbidity, excess mortality, substantial costs, and heightened risk of suicide. MDD is a major cause of disability worldwide. Twin studies attribute ~40% of the variation in liability to MDD to additive genetic effects, and may be greater for recurrent, early-onset, and postpartum MDD. GWA studies of MDD have had notable difficulties in identifying loci. Previous findings suggest that an appropriately designed study should identify susceptibility loci. Methods We conducted a Genome-Wide Association (GWA) meta-analysis in 130,664 MDD cases and 330,470 controls. We used the standard GWA mega/meta-analysis methods of the core PGC quality control, imputation, and analysis pipeline (i.e., ricopili) Results We identified 44 independent loci that met criteria for statistical significance. We can make a strong case for the identification of RBFOX1 and NEGR1. The genetic findings were associated with clinical features of MDD, and implicated prefrontal and anterior cingulate cortex in the pathophysiology of MDD (regions exhibiting anatomical differences in MDD cases vs controls). Genes that are targets of antidepressant medications were strongly enriched for MDD association signals (P=8.5e-10), suggesting the relevance of these findings for improved pharmacotherapy of MDD. Sets of genes involved in gene splicing and in creating isoforms were also enriched for smaller MDD GWA P-values, and these gene sets have also been implicated in schizophrenia and autism. Genetic risk for MDD was correlated with that for many adult and childhood onset psychiatric disorders. Our analyses suggested important relations of genetic risk for MDD with educational attainment, body mass, and schizophrenia: the genetic basis of lower educational attainment and higher body mass were putatively causal for MDD whereas MDD and schizophrenia reflected a partly shared biological etiology. Discussion We present extensive analyses of these results which provide new insights into the nature of MDD. All humans carry lesser or greater numbers of genetic risk factors for MDD, and a continuous measure of risk underlies the observed clinical phenotype. MDD is not a distinct entity that neatly demarcates normalcy from pathology but rather a useful clinical construct associated with a range of adverse outcomes and the end result of a complex process of intertwined genetic and environmental effects. These findings help refine and define the fundamental basis of MDD.

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women.

Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities. The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined. European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case-control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity. The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

Plasma BDNF Level in Major Depression: Biomarker of the Val66Met BDNF Polymorphism and of the Clinical Course in Met Carrier Patients

Aims: Despite the involvement of the brain-derived neurotrophic factor (BDNF) in the physiopathology of major depressive disorder (MDD), the coherence between the components of the BDNF pathway and their link with the clinical features of MDD are insufficiently studied. We aimed to assess in Caucasian depressed patients the impact of the BDNF Val66Met polymorphism on plasma BDNF levels taking into account the clinical characteristics of MDD. Methods: A total of 328 Caucasian adult MDD patients with a current major depressive episode (MDE) were assessed for the BDNF Val66Met polymorphism, plasma BDNF levels and clinical characteristics of the MDD. Results: Plasma BDNF levels were linearly associated with the BDNF Val66Met genotypes (ValVal: 1,525.9 ± 1,183.3 pg/mL vs. ValMet: 1,248.7 ± 1,081.8 vs. MetMet: 1,004.9 ± 952.8; p = 0.04), Met carriers having lower BDNF levels than ValVal ones. Significant interactions between the Val66Met polymorphism and 3 clinical characteristics - age at onset (p = 0.03), MDD duration (p = 0.04), and number of previous MDE (p = 0.04) - were evidenced for plasma BDNF levels. Indeed, in Met carriers, but not in ValVal ones, plasma BDNF levels were negatively correlated with age at onset and positively correlated with MDD duration and number of previous MDE. Conclusion: Our results show a measurable, coherent, and functional BDNF pathway based on the BDNF Val66Met polymorphism and plasma BDNF levels in patients with a current MDE. This pathway is related to the clinical course of major depression, plasma BDNF levels being associated with the long-term history of MDD in Met carriers. Further studies assessing central BDNF are needed to understand the underlying mechanisms of this association.

Neuron-specific enolase levels in drug-naïve young adults with major depressive disorder

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18–29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults.

Smoking and major depressive disorder in Chinese women.

ObjectiveTo investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers.MethodsWe examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status.ResultsAmong the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence.ConclusionsAlthough depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors.

Altered brain network modules induce helplessness in major depressive disorder

ObjectiveThe abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. MethodsResting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. ResultsSmall-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. LimitationThe limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. ConclusionsThe results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness.

Neurotrophic factors, clinical features and gender differences in depression.

Recent studies have evaluated the role of brain-derived neurotrophic factor (BDNF) in mood disorders; however, little is known about alterations in nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). The aim of this study was to evaluate differences among serum neurotrophic factors (BDNF, NGF and GDNF) in depressed patients and healthy controls and to verify the association between serum neurotrophic levels and clinical characteristics in a young, depressed population stratified by gender. This is a cross-sectional study with depressed patients and population controls 18-29years of age. The concentrations of neurotrophic factors were determined by the ELISA method. The diagnosis of depression and the duration of the disease were assessed by the Structured Clinical Interview according to the diagnostic and statistical manual of mental disorders. Depression severity was measured with the 17-item Hamilton Rating Scale for Depression, and the severity of anxiety symptoms was measured using the Hamilton Anxiety Rating Scale. Serum BDNF and GDNF were lower in major depressive disorder (MDD) patients compared to controls (p≤0.001). Serum NGF levels were higher in MDD patients versus controls (p≤0.001). BDNF was associated with the duration of disease only in women (p=0.005). GDNF was not associated with clinical characteristics in either gender. In women, NGF was associated with the severity of depressive symptoms (p=0.009), anxiety (p=0.011) and disease duration (p=0.005). NGF was associated with disease duration in men (p=0.026). Our results demonstrated that significant neurochemical differences in NGF and BDNF, but not in GDNF, were associated with the clinical features of MDD when patients were stratified by gender.

Adjunctive Tai Chi in Geriatric Depression With Comorbid Arthritis: A Randomized, Controlled Trial

Depression in older adults is common, persistent, and disabling. Major depressive disorder (MDD) and arthritis pain disorders co-occur in 25-40% of the population and are associated with reduced adherence to and effectiveness of pain management treatments. Biomarkers such as inflammatory cytokines and neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF) influence neural substrates in late-life depression. Elevated levels of inflammatory cytokines have been linked to anhedonia, cognitive dysfunction, neurovegetative changes, and enhanced pain sensitivity which are clinical features of MDD.

MAJOR DEPRESSIVE DISORDER IN VULNERABLE GROUPS OF OLDER ADULTS, THEIR COURSE AND TREATMENT, AND PSYCHIATRIC COMORBIDITY

Although a number of epidemiology studies of major depressive disorder (MDD) in older adults have been reported, most of them suffer four limitations: (1) the sample was not nationally representative; (2) the sample was relatively small or only one or two sociodemographic correlates of MDD were examined; (3) psychiatric comorbidity was not examined; and (4) the clinical characteristics of MDD were not reported. This study (1) examines the prevalence of DSM-IV MDD across different demographics, especially the vulnerable ones; (2) identifies clinical characteristics of DSM-IV MDD, such as onset, course, and treatment; and (3) evaluates the comorbidity of DSM-IV MDD with anxiety disorder, substance-use disorder, and personality disorder. We analyzed data on 8,205 individuals aged 65 or older from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a nationally representative survey of the noninstitutionalized U.S. household population. The Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version assessed MDD, anxiety, substance use, personality disorders, and pathological gambling. The survey also included demographic characteristics: age, sex, race/ethnicity, marital status, education, employment status, personal income, urban vs. rural residence, and region of the country. Marital status and gender were associated with MDD, whereas race and socioeconomic characteristics were not. Specifically, the prevalence rates of past-year MDD were significant greater for females (3.6%) than males (2.0%) and higher for widowed (4.9%) or separated/divorced (3.5%) than married (1.85%). The mean onset age was 50 years and the average number of lifetime episodes was 4.4. Only half of older adults with MDD had received treatment, even though one-fourth had thought about suicide. Anxiety disorder, substance dependence, and pathological gambling were highly associated with MDD. Prevention could be targeted to older women and those who were widowed, separated, or divorced and low treatment rate was also alarming. More research is needed for the comorbid psychiatric disorders in late-life depression because of their impact on the course and prognosis of MDD.

The impact of educational status on the clinical features of major depressive disorder among Chinese women

BackgroundYears of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting.MethodsClinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD.ResultsSubjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide.LimitationsFindings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample.ConclusionsThe relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD.

Ask the Expert Psychopharmacology: Major depressive disorder

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P4.021 Robust response to memantine treatmentwhen functional and behavioral results are combined with cognition

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18–29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults.

Prefrontal-subcortical and limbic circuit mediation of major depressive disorder.

Substantial progress has been made in elucidating the pathophysiology of major depressive disorder (MDD) using functional and structural brain imaging. In functional imaging studies comparing MDD subjects to normal controls at baseline, dorsolateral prefrontal cortex (DLPFC) activity has been found to be decreased and ventrolateral prefrontal cortex (VLPFC) activity has been found to be increased in MDD. Other regions found abnormal in baseline studies include the anterior cingulate gyrus (AC), temporal lobe, and basal ganglia. Studies examining mood state change (using sleep deprivation, sadness-induction, and tryptophan depletion) and changes from pre- to posttreatment have generally shown improvement of these abnormalities with improved MDD symptoms and worsening of these abnormalities with worsening symptoms. In structural imaging studies, decreased frontal lobe, hippocampal, and basal ganglia volumes are the most commonly reported findings. Several associations can be made between clinical features of MDD and brain function: (1) active sad thoughts/sadness with both decreased DLPFC and dorsal AC activity and increased VLPFC and ventral AC activity (2) psychomotor retardation with decreased left prefrontal activity (3) anxiety with increased left AC activity (4) impaired episodic memory with left prefrontal and medial temporal dysfunction and (5) impaired sustained attention with right prefrontal and parietal dysfunction.