Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference during an Affective Go/No-Go Task.

Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11-18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD.

Functional MRI of emotional memory in adolescent depression.

INTRODUCTION: Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. Mood-congruent biases in memory tasks are frequently reported in MDD patients, with facilitated memory for negative stimuli. Most functional MRI studies to date have examined the neural correlates of these biases in depressed adults, with fewer studies in adolescents with MDD. Investigation of MDD in adolescence may aid greater understanding of the aetiology and development of the disorder. METHODS: Cognitive biases were investigated in 56 MDD patients aged 11-17 years and a matched group of 30 healthy control participants with a self-referential memory task. Behavioural performance and BOLD fMRI data were collected during both encoding and retrieval stages. RESULTS: The neural response to encoding in adolescents with MDD was found to differ significantly from controls. Additionally, neural responses during encoding and retrieval showed differential relationships with age between patient and control groups, specifically in medial, temporal, and prefrontal regions. CONCLUSIONS: These findings suggest that during adolescence neurophysiological activity associated with emotional memory differs in those with depression compared to controls and may be age sensitive.

Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents.

BACKGROUND: Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. METHODS: Eighty-two Depressed and 24 healthy female adolescents, aged 12-17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. RESULTS: At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. LIMITATIONS: In the follow-up section, a limited number of post-CBT patients were recruited. CONCLUSIONS: To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

OBJECTIVE: There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. METHOD: Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. RESULTS: Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. CONCLUSIONS: The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance-Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT).

BACKGROUND: Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. METHODS/DESIGN: Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). DISCUSSION: MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response. TRIAL REGISTRATION: Adjunctive study to IMPACT trial (Current Controlled Trials: ISRCTN83033550).

A double-blind, placebo-controlled study of the impact of galantamine on anterograde memory impairment during electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) continues to be an effective treatment option for patients who fail to respond to pharmacological interventions, are unable to tolerate medications, and show a suboptimal response to behavioral and psychotherapeutic treatments. However, risks for cognitive impairment may contribute to some patients' refusal of ECT. METHODS: The present study examined galantamine as a pharmacological intervention to reduce cognitive adverse effects from ECT. Thirty-nine inpatients diagnosed with major depressive disorder; bipolar disorder, depressed type; or schizoaffective disorder, depressed type and admitted for ECT were randomized to galantamine or placebo. Study drugs were initiated 24 to 48 hours before starting ECT and continued throughout the course of ECT. A neuropsychological test battery was administered at baseline and 24 to 48 hours after completing a course of ECT treatments. Depression severity was monitored using the 17-item Hamilton Rating Scale for Depression and Clinical Global Impression Scale at baseline, weekly, and end point. Self-rated adverse effects were monitored weekly. RESULTS: Thirty participants (12 patients in the galantamine group, 18 patients in the placebo group) had both pretreatment and posttreatment neuropsychological ratings. Those in the galantamine group scored significantly higher at discharge for delayed memory (t28 = 2.44, P < 0.05). Hierarchical regressions examined if treatment condition predicted changes in delayed memory scores from baseline to discharge. Inclusion of the treatment condition in the final model made a significant incremental improvement in prediction (ΔR = 0.12, F1,27 change = 4.65, P < 0.05; ß = 0.37, t = 2.16, P < 0.05). Galantamine was well tolerated with no clinically significant bradycardia or prolonged paralysis when administered with ECT. CONCLUSIONS: Galantamine may be protective against impairment in retention of new learning. Galantamine exhibited minimal adverse effects and was safe when administered during ECT. The present findings require replication by future researchers using larger samples before broad conclusions can be drawn.

Evidence for the diagnostic criteria of delirium: an update.

PURPOSE OF REVIEW: Since the publication of DSM-III in 1980, the essential criteria for delirium have been reduced progressively through DSM-III-R to DSM-IV. As the field moves toward DSM-V and ICD-11, new data can shed light on the nosological changes that are needed so that diagnostic criteria can reflect empirical data. In this study, we reassess the existing or potential criteria for delirium. RECENT FINDINGS: Phenomenological studies in recent years have informed the criteria for delirium, including the appropriateness of the term 'consciousness' as a core symptom of the diagnosis, additional symptoms of delirium that are frequent but are not currently part of the diagnostic criteria, subsyndromal delirium, motoric subtypes of delirium (hyperactive, hypoactive), and the association of delirium with dementia. SUMMARY: Recent studies suggest that motoric subtypes should be included as a subtype for delirium but that subsyndromal delirium, although a useful research construct, should not be included in clinical diagnostic criteria given the frequent fluctuation in symptoms over short periods. In addition, though the core symptoms are probably adequate to make the diagnosis, clinicians must be aware of the frequency of other symptoms, for symptoms such as profound sleep disturbance or psychotic symptoms may dominate the clinical picture.

Changes in depressive symptoms and social functioning in the sequenced treatment alternatives to relieve depression study.

Major depressive disorder (MDD) profoundly affects social functioning, including the ability to enjoy social activities with peers, friends, and family members. We sought to compare changes in social functioning and depressive symptoms in the first level of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Adult outpatients (N = 2876) with diagnoses of MDD were treated using flexible doses of citalopram for up to 14 weeks. We compared the change over the course of treatment in the social activities item of the Work and Social Adjustment Scale to the change in individual items of the Quick Inventory of Depressive Symptoms-Self-Rated (QIDS-SR). Improvement in social functioning was modestly positively correlated with improvement in sad mood, concentration/decision making, involvement, and energy/fatigability. Only 16% to 22% of the variance in the change in social functioning was accounted for by these symptoms, and only 32% was accounted for by the total QIDS-SR score. In this large real-world sample of outpatients treated using citalopram, changes in depressive symptoms do not entirely explain improvements in social functioning.

An open study of aripiprazole and escitalopram for psychotic major depressive disorder.

OBJECTIVE: This 7-week trial assessed the efficacy and tolerability of aripiprazole combined with escitalopram in the acute treatment of major depressive disorder, with psychotic features (MD-Psy). METHODS: Sixteen male and female patients with a Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of MD-Psy were recruited for this study from September 13, 2004 to August 9, 2006. Escitalopram and aripiprazole were flexibly dosed for 7 weeks, with maximum dosages of 20 and 30 mg/d, respectively. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Structured Clinical Interview for DSM-IV psychosis module were used to measure depression and psychosis responses. The Barnes Akathisia Scale and the Simpson Angus Scale were used to assess for akathisia and extrapyramidal symptoms. RESULTS: Thirteen of the 16 subjects completed the study. The MD-Psy response rate (50% or greater drop in HAM-D-17 and no psychosis) (intent-to-treat, last observation carried forward) was 62.5%, and the MD-Psy remission rate (HAM-D-17, <8, and no psychosis) (intent-to-treat, last observation carried forward) was 50.0%. Ten of the 16 subjects developed akathisia; however, 9 of the 10 subjects had resolution or partial resolution of akathisia with dose adjustment or treatment with propranolol. CONCLUSIONS: The combination of escitalopram and aripiprazole seems to be an effective and safe treatment for MD-Psy.