The protective effects of Swedish COVID-19 pandemic strategies on adolescents' mental health: a longitudinal cohort study.

AIM: The aim of this study was to investigate a cohort of Swedish eighth graders' mental health and experiences during the COVID-19 pandemic. METHODS: Participants were 157 eighth graders recruited in junior high schools during 2020 who completed a depression questionnaire and a survey about their psychosocial health in relation to the COVID-19 pandemic, alongside a follow-up assessment in 2021. Analyses were conducted using latent change score and cross-lagged models. RESULTS: Participants' depressive symptoms did not substantially increase during the COVID-19 pandemic. The level of depressive symptoms in 2020 was significantly associated with participants' perceptions of the pandemic in 2020 and spring 2021. Participants with higher depression scores reported worse experiences of the pandemic. CONCLUSIONS: The stable level of depressive symptoms among this cohort of eighth graders suggested that keeping schools open during a nationwide lockdown could mitigate some mental health consequences. Adolescents in this study with higher self-assessed depressive symptoms were more likely to experience increased depression after 6 months and had worse experiences during the pandemic than others. This suggests that the pandemic may not immediately affect mental well-being, but those at risk may be affected over time.

Metabolomic and inflammatory signatures of symptom dimensions in major depression.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions. METHODS: Using three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism. RESULTS: The IMD clinical dimension and the inflammatory index were positively correlated (r = 0.19, p = 0.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids. CONCLUSION: The IMD dimension of depression appears reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.

ERICH3: vesicular association and antidepressant treatment response.

Selective serotonin reuptake inhibitors (SSRIs) are standard of care for major depressive disorder (MDD) pharmacotherapy, but only approximately half of these patients remit on SSRI therapy. Our previous genome-wide association study identified a single-nucleotide polymorphism (SNP) signal across the glutamate-rich 3 (ERICH3) gene that was nearly genome-wide significantly associated with plasma serotonin (5-HT) concentrations, which were themselves associated with SSRI response for MDD patients enrolled in the Mayo Clinic PGRN-AMPS SSRI trial. In this study, we performed a meta-analysis which demonstrated that those SNPs were significantly associated with SSRI treatment outcomes in four independent MDD trials. However, the function of ERICH3 and molecular mechanism(s) by which it might be associated with plasma 5-HT concentrations and SSRI clinical response remained unclear. Therefore, we characterized the human ERICH3 gene functionally and identified ERICH3 mRNA transcripts and protein isoforms that are highly expressed in central nervous system cells. Coimmunoprecipitation identified a series of ERICH3 interacting proteins including clathrin heavy chain which are known to play a role in vesicular function. Immunofluorescence showed ERICH3 colocalization with 5-HT in vesicle-like structures, and ERICH3 knock-out dramatically decreased 5-HT staining in SK-N-SH cells as well as 5-HT concentrations in the culture media and cell lysates without changing the expression of 5-HT synthesizing or metabolizing enzymes. Finally, immunofluorescence also showed ERICH3 colocalization with dopamine in human iPSC-derived neurons. These results suggest that ERICH3 may play a significant role in vesicular function in serotonergic and other neuronal cell types, which might help explain its association with antidepressant treatment response.

Anxiety and Depression from Childhood to Young Adulthood: Trajectories and Risk Factors.

This study aimed to (1) evaluate how population levels of anxiety and depression grow and correlate from middle childhood through early adulthood, and (2) determine whether sex, family socioeconomic status, parental education, academic achievement, learning disabilities, or externalizing symptoms predict anxiety and/or depression levels and growth trajectory. We used two longitudinal samples (N = 445, 448) of Portuguese children. Mean depression levels increased from mid-childhood through adolescence before stabilizing in early adulthood and were most strongly predicted by academic achievement and learning disabilities. Mean anxiety levels increased until adolescence before decreasing across early adulthood and were most strongly predicted by academic achievement, learning disabilities, and externalizing symptoms. Quadratic models of growth fit best for both depression and anxiety, and depression and anxiety growth trajectories were strongly correlated. Though anxiety and depression trajectories differ in pattern and predictors, the two are highly interrelated and pathways to comorbid anxiety and depression should be characterized.

Reliability and Validity of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Portuguese Version.

This study examined the test-retest reliability, consensual, convergent and divergent validities, sensitivity, specificity, positive and negative predictive values, and accuracy of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Eighty-nine children/adolescents (65 psychiatric outpatients and 24 healthy controls) were interviewed with K-SADS-PL and completed measures of depressive and anxiety symptoms. The child's parent/caretaker completed the Child Behavior Checklist. Good to excellent values were obtained for test-retest reliability and consensual validity. For the convergent validity, moderate correlations between the K-SADS-PL and the corresponding self-report measures were observed. Divergent validity was acceptable for the K-SADS-PL diagnoses. The lowest values of sensitivity, specificity, and accuracy of the K-SADS-PL were 88, 88, and 91, respectively. The Portuguese version of K-SADS-PL proved to be a valid and reliable assessment instrument for children and adolescents, and was sensitive, specific and accurate when diagnosing mood, anxiety, adjustment, and attention-deficit/hyperactivity disorders.

Psychotherapy or medication for depression? Using individual symptom meta-analyses to derive a Symptom-Oriented Therapy (SOrT) metric for a personalised psychiatry.

BACKGROUND: Antidepressant medication (ADM) and psychotherapy are effective treatments for major depressive disorder (MDD). It is unclear, however, if treatments differ in their effectiveness at the symptom level and whether symptom information can be utilised to inform treatment allocation. The present study synthesises comparative effectiveness information from randomised controlled trials (RCTs) of ADM versus psychotherapy for MDD at the symptom level and develops and tests the Symptom-Oriented Therapy (SOrT) metric for precision treatment allocation. METHODS: First, we conducted systematic review and meta-analyses of RCTs comparing ADM and psychotherapy at the individual symptom level. We searched PubMed Medline, PsycINFO, and the Cochrane Central Register of Controlled Trials databases, a database specific for psychotherapy RCTs, and looked for unpublished RCTs. Random-effects meta-analyses were applied on sum-scores and for individual symptoms for the Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) measures. Second, we computed the SOrT metric, which combines meta-analytic effect sizes with patients' symptom profiles. The SOrT metric was evaluated using data from the Munich Antidepressant Response Signature (MARS) study (n = 407) and the Emory Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study (n = 234). RESULTS: The systematic review identified 38 RCTs for qualitative inclusion, 27 and 19 for quantitative inclusion at the sum-score level, and 9 and 4 for quantitative inclusion on individual symptom level for the HAM-D and BDI, respectively. Neither meta-analytic strategy revealed significant differences in the effectiveness of ADM and psychotherapy across the two depression measures. The SOrT metric did not show meaningful associations with other clinical variables in the MARS sample, and there was no indication of utility of the metric for better treatment allocation from PReDICT data. CONCLUSIONS: This registered report showed no differences of ADM and psychotherapy for the treatment of MDD at sum-score and symptom levels. Symptom-based metrics such as the proposed SOrT metric do not inform allocation to these treatments, but predictive value of symptom information requires further testing for other treatment comparisons.

Common genes associated with antidepressant response in mouse and man identify key role of glucocorticoid receptor sensitivity.

Response to antidepressant treatment in major depressive disorder (MDD) cannot be predicted currently, leading to uncertainty in medication selection, increasing costs, and prolonged suffering for many patients. Despite tremendous efforts in identifying response-associated genes in large genome-wide association studies, the results have been fairly modest, underlining the need to establish conceptually novel strategies. For the identification of transcriptome signatures that can distinguish between treatment responders and nonresponders, we herein submit a novel animal experimental approach focusing on extreme phenotypes. We utilized the large variance in response to antidepressant treatment occurring in DBA/2J mice, enabling sample stratification into subpopulations of good and poor treatment responders to delineate response-associated signature transcript profiles in peripheral blood samples. As a proof of concept, we translated our murine data to the transcriptome data of a clinically relevant human cohort. A cluster of 259 differentially regulated genes was identified when peripheral transcriptome profiles of good and poor treatment responders were compared in the murine model. Differences in expression profiles from baseline to week 12 of the human orthologues selected on the basis of the murine transcript signature allowed prediction of response status with an accuracy of 76% in the patient population. Finally, we show that glucocorticoid receptor (GR)-regulated genes are significantly enriched in this cluster of antidepressant-response genes. Our findings point to the involvement of GR sensitivity as a potential key mechanism shaping response to antidepressant treatment and support the hypothesis that antidepressants could stimulate resilience-promoting molecular mechanisms. Our data highlight the suitability of an appropriate animal experimental approach for the discovery of treatment response-associated pathways across species.

Somatic symptoms in treatment-naïve Hispanic and non-Hispanic patients with major depression.

BACKGROUND: Somatic complaints are a major driver of health care costs among patients with major depressive disorder (MDD). Some epidemiologic and clinical data suggest that Hispanic and non-Hispanic Black patients with MDD endorse higher levels of somatic symptoms than non-Hispanic White patients. METHODS: Somatic symptoms in 102 Hispanic, 61 non-Hispanic Black, and 156 non-Hispanic White patients with treatment-naïve MDD were evaluated using the somatic symptom subscale of the Hamilton anxiety rating scale (HAM-A). The other seven items of the HAM-A comprise the psychic anxiety subscale, which was also evaluated across ethnicities. RESULTS: Hispanic patients reported significantly greater levels of somatic symptoms than non-Hispanic patients, but levels of psychic anxiety symptoms did not differ by ethnicity. Levels of somatic symptoms did not significantly differ between Black and White non-Hispanic patients. Within the Hispanic sample, somatic symptom levels were higher only among those who were evaluated in Spanish; Hispanics who spoke English showed no significant differences versus non-Hispanics. CONCLUSIONS: In this medically healthy sample of patients with MDD, monolingual Spanish-speaking Hispanic patients endorsed high levels of somatic symptoms. Clinicians should be mindful that the depressive experience may manifest somatically and be judicious in determining when additional medical work-up is warranted for somatic complaints.

Suicidal ideation and other persisting symptoms after CBT or antidepressant medication treatment for major depressive disorder.

BACKGROUND: Persisting symptoms after treatment for major depressive disorder (MDD) contribute to ongoing impairment and relapse risk. Whether cognitive behavior therapy (CBT) or antidepressant medications result in different profiles of residual symptoms after treatment is largely unknown. METHODS: Three hundred fifteen adults with MDD randomized to treatment with either CBT or antidepressant medication in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study were analyzed for the frequency of residual symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) item scores at the end of the 12-week treatment period. Separate comparisons were made for treatment responders and non-responders. RESULTS: Among treatment completers (n = 250) who responded to CBT or antidepressant medication, there were no significant differences in the persistence of residual MADRS symptoms. However, non-responders treated with medication were significantly less likely to endorse suicidal ideation (SI) at week 12 compared with those treated with CBT (non-responders to medication: 0/54, 0%, non-responders to CBT: 8/30, 26.7%; p = .001). Among patients who terminated the trial early (n = 65), residual MADRS item scores did not significantly differ between the CBT- and medication-treated groups. CONCLUSIONS: Depressed adults who respond to CBT or antidepressant medication have similar residual symptom profiles. Antidepressant medications reduce SI, even among patients for whom the medication provides little overall benefit.

Response rate profiles for major depressive disorder: Characterizing early response and longitudinal nonresponse.

BACKGROUND: Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based on their rate of change over time, while simultaneously addressing the issue of controlling for baseline severity. METHODS: A set of latent class trajectory analyses, incorporating baseline level of symptoms, were performed on a sample of 344 depressed patients from a clinical trial evaluating the efficacy of cognitive behavior therapy and two antidepressant medications (escitalopram and duloxetine) in patients with major depressive disorder. RESULTS: Although very few demographic and illness-related features were associated with response rate profiles, the aggregated effect of candidate genetic variants previously identified in large pharmacogenetic studies and meta-analyses showed a significant association with early remission as well as nonresponse. These same genetic scores showed a less compelling relationship with endpoint response categories. In addition, consistent nonresponse throughout the study treatment period was shown to occur in different subjects than endpoint nonresponse, which was verified by follow-up augmentation treatment outcomes. CONCLUSIONS: When defining groups based on the rate of change, controlling for baseline depression severity may help to identify the clinically relevant distinctions of early response on one end and consistent nonresponse on the other.

Preliminary Findings Supporting Insula Metabolic Activity as a Predictor of Outcome to Psychotherapy and Medication Treatments for Depression.

A putative right anterior insula metabolism biomarker predictive of treatment outcomes was retrospectively applied to 30 depressed psychotherapy--or escitalopram-treated nonremitters who entered combination treatment. Patients whose added treatment matched the biomarker-indicated treatment remitted more often than biomarker-mismatched patients.

Combination psychotherapy and antidepressant medication treatment for depression: for whom, when, and how.

Major depressive disorder (MDD) is among the most frequent and debilitating psychiatric disorders. Efficacious psychotherapy and antidepressant medications have been developed, and two-thirds of depressed patients respond to single-modality treatment; however, only about one-third of patients remit to single-modality treatments with no meaningful differences in outcomes between treatment types. This article describes the major clinical considerations in choosing between single-modality or combination treatments for MDD. A review of the relevant literature and meta-analyses provides suggestions for which treatment to use for which patient and when each treatment or combination should be provided. The review summarizes the moderators of single-modality and combination-treatment outcomes. We describe models of mechanisms of treatment efficacy and discuss recent treatment-specific neurobiological mechanisms of change.

Parental relationships and behavioral approach system dysregulation in young adults with bipolar disorder.

OBJECTIVES: Expressed emotion (EE), or the presence of criticism/hostility/emotional overinvolvement in a family relationship, predicts poorer outcomes in bipolar disorder; however, the mechanism of this is unclear. The present study investigated whether, in a sample of young adults (aged 18-40 years) with bipolar disorder, parental criticism was associated with Behavioral Approach System (BAS) dysregulation, including emotional reactivity to negative feedback and cognitive schemas of self-criticism/perfectionism. METHOD: Twenty-two young adults with bipolar I disorder and 22 matched control participants completed an interview, questionnaires, and a computer-based task with false negative feedback; emotional reactivity to this feedback was assessed. RESULTS: Compared to control participants, clinical participants exhibited higher levels (p = 0.001) of self-criticism, and a trend towards a greater decrease in positive affect after negative feedback (p = 0.053), even when controlling for mood symptoms. Among clinical participants, perceived criticism from paternal caregivers was associated with self-criticism and perfectionism, and low perceived paternal care was associated with decrease in positive affect. CONCLUSION: Strain in parental relationships may be associated with BAS dysregulation for individuals with bipolar disorder.

Enhancing Hispanic participation in mental health clinical research: development of a Spanish-speaking depression research site.

BACKGROUND: Hispanics, particularly those with limited English proficiency, are underrepresented in psychiatric clinical research studies. We developed a bilingual and bicultural research clinic dedicated to the recruitment and treatment of Spanish-speaking subjects in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study, a large clinical trial of treatment-naïve subjects with major depressive disorder (MDD). METHODS: Demographic and clinical data derived from screening evaluations of the first 1,174 subjects presenting for participation were compared between the Spanish-speaking site (N = 275) and the primary English-speaking site (N = 899). Reasons for ineligibility (N = 888) for the PReDICT study were tallied for each site. RESULTS: Compared to English speakers, Spanish speakers had a lower level of education and were more likely to be female, uninsured, and have uncontrolled medical conditions. Clinically, Spanish speakers demonstrated greater depression severity, with higher mean symptom severity scores, and a greater number of previous suicide attempts. Among the subjects who were not randomized into the PReDICT study, Spanish-speaking subjects were more likely to have an uncontrolled medical condition or refuse participation, whereas English-speaking subjects were more likely to have bipolar disorder or a non-MDD depressive disorder. CONCLUSION: Recruitment of Hispanic subjects with MDD is feasible and may enhance efforts at signal detection, given the higher severity of depression among Spanish-speaking participants presenting for clinical trials. Specific approaches for the recruitment and retention of Spanish-speaking participants are required.

Impact of sleep complaints and depression outcomes among participants in the standard medical intervention and long-term exercise study of exercise and pharmacotherapy for depression.

The aim of this study was to examine the effects of exercise and sertraline on disordered sleep in patients with major depressive disorder (MDD). Methods The Standard Medical Intervention and Long-term Exercise study randomized the patients with MDD (n = 202) to one of four arms: a) supervised exercise, b) home-based exercise, c) sertraline therapy, and d) placebo pill. Sleep disturbance was assessed with three sleep-related items from the Hamilton Rating Scale for Depression (HAM-D) before and after 4 months of treatment. The patients were followed for 12 months to assess the prognostic value of sleep disturbance on MDD relapse and recovery.Results Comparison of the active treatment and placebo groups showed no treatment differences in HAM-D sleep complaints after 4 months (p = 0.758). However, residual insomnia symptoms after treatment were strongly associated with elevated depressive symptoms assessed by the HAM-D after 4 months (ß = 0.342, p < 0.0001) and MDD relapse (odds ratio, 1.55; 95% confidence interval, 1.15-2.10; p = 0.004) assessed at 1-year follow-up (16 months after randomization). Neither exercise nor sertraline was associated with greater improvements in sleep disturbance compared with the placebo controls. However, residual symptoms of insomnia after successful treatment of MDD predicted relapse, highlighting the clinical importance of addressing insomnia in patients with MDD.

Personality pathology factors predict recurrent major depressive disorder in emerging adults.

OBJECTIVE: Prior investigations consistently indicate that personality pathology is a risk factor for recurrence of major depressive disorder (MDD). Lack of emipircal support, however, for the Diagnostic and Statistical Manual of Mental Disorders (DSM) Fourth Edition organization of Axis II disorders supports the investigation of empirically derived factors of personality pathology as predictors of recurrence. METHOD: A sample of 130 previously depressed emerging adults (80% female; aged 18 to 21 years) were assessed for personality disorder symptoms at baseline. Participants were then followed for 18 months to identify MDD recurrence during the first 2 years of college. RESULTS: Based on a previous factor analysis of DSM personality disorder criteria, eight personality pathology factors were examined as predictors of MDD recurrence. Survival analysis indicated that factors of interpersonal hypersensitivity, antisocial conduct, and social anxiety were associated with increased risk of MDD recurrence. CONCLUSIONS: These findings suggest that an empirically based approach to personality pathology organization may yield useful predictors of MDD recurrence during emerging adulthood.

The utility of measuring daily hassles and uplifts in understanding outcomes to treatments for major depressive disorder.

Little is known about the effects of common daily experiences in patients with major depressive disorder (MDD). The Daily Hassles and Uplifts Scale (HUPS) was assessed in 142 treatment-naïve adult MDD outpatients randomized to 12 weeks of treatment with either antidepressant medication (ADM) or Cognitive Behavior Therapy (CBT). Three HUPS measures were analyzed: hassle frequency (HF), uplift frequency (UF), and the mean hassle intensity to mean uplift intensity ratio (MHI:MUI). Remission after treatment was not predicted by these baseline HUPS measures and did not moderate outcomes by treatment type. In contrast, HUPS measures significantly changed with treatment and were impacted by remission status. Specifically, HF and MHI:MUI decreased and UF increased from baseline to week 12, with remission leading to significantly greater decreases in HF and MHI:MUI compared to non-remission. ADM-treated patients demonstrated significant improvements on all three HUPS measures regardless of remission status. In contrast, remitters to CBT demonstrated significant improvements in HF and MHI:MUI but not UF; among CBT non-remitters the only significant change was a reduction in HF. The changes in HUPS measures are consistent with how affective biases are impacted by treatments and support the potential value of increasing attention to positive events in CBT.

Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavior Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder.

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways. Changes in metabolite concentrations related to each treatment arm were identified and compared to define metabolic signatures of exposure. In addition, association between metabolites and depressive symptom severity (assessed with the 17-item Hamilton Rating Scale for Depression [HRSD17]) and anxiety symptom severity (assessed with the 14-item Hamilton Rating Scale for Anxiety [HRSA14]) were evaluated, both at baseline and after 12 weeks of treatment. Significant reductions in serum serotonin level and increases in tryptophan-derived indoles that are gut bacterially derived were observed with escitalopram and duloxetine arms but not in CBT arm. These include indole-3-propionic acid (I3PA), indole-3-lactic acid (I3LA) and Indoxyl sulfate (IS), a uremic toxin. Purine-related metabolites were decreased across all arms. Different metabolites correlated with improved symptoms in the different treatment arms revealing potentially different mechanisms between response to antidepressant medications and to CBT.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (ß = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Behavioural activation for the treatment of low-income, African American adolescents with major depressive disorder: a case series.

Behavioural activation (BA) is a psychosocial treatment that has shown promise in the treatment of adults suffering from major depressive disorder (MDD). Recent studies have shown that BA may also be effective for treating depressed adolescents. There are no studies that have reported on the BA treatment of depressed and low-income African American adolescents; thus, the current study reports on the effectiveness of a version of BA adapted for the treatment of African American adolescents who were diagnosed with MDD (n = 3). Participants were allowed to attend a maximum of 17 sessions of weekly psychotherapy. Based on results taken from structured interviews, two of the three participants no longer met criteria for MDD at the end of treatment, and the severity of clinician-rated depressive symptoms and impairment decreased for all participants at post-treatment assessment. Additionally, all participants and their caregivers reported satisfaction with treatment. Implications of these findings, study limitations and suggestions for future directions are discussed.