Treatment Remitters Research Articles

Smartphone application-delivered cognitive behavioural therapy for insomnia with telephone support for insomnia disorder compared to a waitlist control: a randomised clinical trial.

Although there have been promising findings for smartphone application (app)-delivered cognitive behavioural therapy for insomnia (CBT-I), previous trials have not screened participants rigorously for insomnia disorder and used therapist support. Based on the above, we aimed to examine the effects of smartphone app-delivered CBT-I with telephone support against a waitlist (WL) in a sample with insomnia disorder. A total of 64 participants with insomnia disorder were randomised to smartphone app-delivered CBT-I (n = 32) or a WL (n = 32). Smartphone app-delivered CBT-I consisted of six weekly smartphone app modules with 15 min of telephone support per week. At pre- and post-treatment, and the 3-month follow-up, we assessed insomnia symptoms and associated correlates and consequences. At post-treatment, we also assessed measures related to adherence (therapist support, exercise/module completion), self-rated perception of treatment content, activity, and adverse events. CBT-I significantly outperformed the WL with large effects on the primary outcome (d = 2.26) and was significantly different on most of the secondary outcomes with medium to large effects. CBT-I also resulted in a significantly larger proportion of treatment remitters (CBT-I: 64.5-77.4%, WL: 6.5-6.9%) and responders (CBT-I: 77.4-90.3%, WL: 19.4-24.1%) at post-treatment and follow-up, compared to the WL. Treatment was associated with high satisfaction, high adherence, low attrition, and few treatment-impeding adverse events. Based on the medium to large effects of smartphone app-delivered CBT-I with telephone support, this trial highlights the potential of delivering CBT-I exclusively through an app with therapist telephone support for high efficacy, satisfaction, and adherence.

Altered task-related decoupling of the rostral anterior cingulate cortex in depression

Dysfunctional activity of the rostral anterior cingulate cortex (rACC) – an extensively connected hub region of the default mode network – has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to characterize functional connectivity of rACC activity suppression (‘deactivation’) – an essential feature of rACC function – during external task engagement in depression. Specifically, we aimed to explore neural patterns of functional decoupling and coupling with the rACC during its task-driven suppression. We enrolled 81 15- to 25-year-old young people with moderate-to-severe major depressive disorder (MDD) before they commenced a 12-week clinical trial that assessed the effectiveness of cognitive behavioral therapy plus either fluoxetine or placebo. Ninety-four matched healthy controls were also recruited. Participants completed a functional magnetic resonance imaging face matching task known to elicit rACC suppression. To identify brain regions associated with the rACC during its task-driven suppression, we employed a seed-based functional connectivity analysis. We found MDD participants, compared to controls, showed significantly reduced ‘decoupling’ of the rACC with extended task-specific regions during task performance. Specifically, less decoupling was observed in the occipital and fusiform gyrus, dorsal ACC, medial prefrontal cortex, cuneus, amygdala, thalamus, and hippocampus. Notably, impaired decoupling was apparent in participants who did not remit to treatment, but not treatment remitters. Further, we found MDD participants showed significant increased coupling with the anterior insula cortex during task engagement. Our findings indicate that aberrant task-related rACC suppression is associated with disruptions in adaptive neural communication and dynamic switching between internal and external cognitive modes that may underpin maladaptive cognitions and biased emotional processing in depression.

A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia

Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response. However, molecular contributions to response across insular regions remain largely unknown. We used 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to measure glutamate (Glu), Glutamine (Gln), and GABA from anterior and posterior regions of the insula across antipsychotic treatment. A total of 36 participants were examined, including 15 individuals with FES and moderate to severe psychosis who were scanned at two time points, while starting and after 6 weeks of antipsychotic treatment. Symptoms were carefully monitored across the study period to characterize treatment response. GABA, Glu, and Gln levels were calculated relative to creatine in anterior and posterior insular regions, bilaterally. In relation to psychotic symptom reduction, we observed a significant increase in Glu across all insular regions with (p < 0.001), but no corresponding changes in Gln or GABA. In group analyses, the FES cohort showed lower levels of Glu (p < 0.001) and GABA (p = 0.02) at baseline. Finally, in exploratory analyses, treatment remitters demonstrated a normalization of lower insular Glu levels across treatment, unlike non-remitters. Overall, these findings contribute to our understating of molecular changes associated with antipsychotic response and demonstrate abnormalities specific to the insula in FES.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials

BackgroundDepression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes.MethodIndividual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators.ResultsItem-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms.ConclusionThe relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

Modulation of inhibitory control networks relate to clinical response following ketamine therapy in major depression

Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD. Forty-seven TRD patients (mean age = 38, 19 women) and 32 healthy controls (mean age = 35, 18 women) performed a functional magnetic resonance imaging (fMRI) response inhibition task at baseline, and 37 patients completed the fMRI task and symptom scales again 24 h after receiving both one and four 0.5 mg/kg intravenous ketamine infusions. Analyses of fMRI data addressed effects of diagnosis, time, and differences between treatment remitters and non-remitters. Significant decreases in brain activation were observed in the inhibitory control network, including in prefrontal and parietal regions, and visual cortex following serial ketamine treatment, p < 0.05 corrected. Remitters were distinguished from non-remitters by having lower functional activation in the supplementary motor area (SMA) prior to treatment, which normalized towards controls following serial ketamine treatment. Results suggest that ketamine treatment leads to neurofunctional plasticity in executive control networks including the SMA during a response-inhibitory task. SMA changes relate to reductions in depressive symptoms, suggesting modulation of this network play an important role in therapeutic response. In addition, early changes in the SMA network during response inhibition appear predictive of overall treatment outcome, and may serve as a biomarker of treatment response.

Modulation of Inhibitory Control Networks Relate to Clinical Response following Ketamine Therapy in Major Depression

Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD. Forty-seven TRD patients (mean age = 38, 19 women) and 32 healthy controls (mean age = 35, 18 women) performed a functional magnetic resonance imaging (fMRI) response inhibition task at baseline, and 37 patients completed the fMRI task and symptom scales again 24 h after receiving both one and four 0.5 mg/kg intravenous ketamine infusions. Analyses of fMRI data addressed effects of diagnosis, time, and differences between treatment remitters and non-remitters. Significant decreases in brain activation were observed in the inhibitory control network, including in prefrontal and parietal regions, and visual cortex following serial ketamine treatment, p < 0.05 corrected. Remitters were distinguished from non-remitters by having lower functional activation in the supplementary motor area (SMA) prior to treatment, which normalized towards controls following serial ketamine treatment. Results suggest that ketamine treatment leads to neurofunctional plasticity in executive control networks including the SMA during a response-inhibitory task. SMA changes relate to reductions in depressive symptoms, suggesting modulation of this network play an important role in therapeutic response. In addition, early changes in the SMA network during response inhibition appear predictive of overall treatment outcome, and may serve as a biomarker of treatment response.

Comparing internet-delivered cognitive therapy and behavior therapy with telephone support for insomnia disorder: a randomized controlled trial.

Study ObjectivesOur aim was to compare the effects of Internet-delivered cognitive therapy (CT) and behavior therapy (BT) against a waitlist (WL) condition to better understand their unique contribution in the treatment of insomnia.MethodsTwo hundred and nineteen participants with insomnia disorder were randomized to CT (n = 72), BT (n = 73), or WL (n = 74). The treatment arms consisted of 10 weekly internet-delivered modules with 15 min of telephone support per week. At pre, post, and follow-up, participants completed measures of insomnia severity, sleep diaries, functional impairment, anxiety, depression, quality of life, adverse events, satisfaction and perception of content, workload, and activity in treatment. Measures of completed exercises, modules, therapist support, and platform logins were also measured at posttreatment.ResultsModerate to large effect sizes for both CT and BT outperformed the WL on the majority of outcomes, with significant differences in favor of both therapy groups. Both treatment groups had significantly larger proportion of treatment remitters (CT: 35.8%, BT: 40%, WL: 2.7%) and responders (CT: 74.6%, BT 58.6%, WL: 10.8%) compared to the WL at posttreatment. There were no significant differences between the two therapy groups in terms of outcomes, except for sleep onset latency in favor of BT (6 min difference at posttreatment) and adverse events in favor of CT (CT 14.1% vs BT 43.2%).ConclusionsThis study indicates that both Internet-delivered CT and BT are effective as stand-alone therapies for insomnia disorder. Results highlight the need for examining which therapy and subcomponents that are necessary for change.ClinicalTrials.gov IdentifierNCT02984670

Depressive Symptom Dimensions in Treatment-Resistant Major Depression and Their Modulation With Electroconvulsive Therapy

Symptom heterogeneity in major depressive disorder obscures diagnostic and treatment-responsive biomarker identification. Whether symptom constellations are differentially changed by electroconvulsive therapy (ECT) remains unknown. We investigate the clustering of depressive symptoms over the ECT index and whether ECT differentially influences symptom clusters. The 17-item Hamilton Depression Rating Scale (HDRS-17) was collected from 111 patients with current depressive episode before and after ECT from 4 independent participating sites of the Global ECT-MRI Research Collaboration. Exploratory factor analysis of HDRS-17 items pre- and post-ECT treatment identified depressive symptom dimensions before and after ECT. A 2-way analysis of covariance was used to determine whether baseline symptom clusters were differentially changed by ECT between treatment remitters (defined as patients with posttreatment HDRS-17 total score ≤8) and nonremitters while controlling for pulse width, titration method, concurrent antidepressant treatment, use of benzodiazepine, and demographic variables. A 3-factor solution grouped pretreatment HDRS-17 items into core mood/anhedonia, somatic, and insomnia dimensions. A 2-factor solution best described the symptoms at posttreatment despite poorer separation of items. Among remitters, core mood/anhedonia symptoms were significantly more reduced than somatic and insomnia dimensions. No differences in symptom dimension trajectories were observed among nonremitting patients. Electroconvulsive therapy targets the underlying source of depressive symptomatology and may confer differential degrees of improvement in certain core depressive symptoms. Our findings of differential trajectories of symptom clusters over the ECT index might help related predictive biomarker studies to refine their approaches by identifying predictors of change along each latent symptom dimension.

Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder.

To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.

Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.

BackgroundChronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations.Methods/designThis is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment acceptability. Centrally trained therapists will administer therapies according to manualized, albeit flexible, treatment algorithms.DiscussionThis clinical trial will provide new information about optimal treatment sequencing and will have direct implication for the development of clinical guidelines for managing chronic insomnia with and without comorbid psychiatric conditions.Trial RegistrationClinicalTrials.gov Identifier: NCT01651442, Protocol version 4, 20 April 2011, registered 26 June 2012

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression.

White matter hyperintensities (WMHs) have been shown to be associated with the development of late-life depression (LLD) and eventual treatment outcomes. This study sought to investigate longitudinal WMH changes in patients with LLD during a 12-week antidepressant treatment course. Forty-seven depressed elderly patients were included in this analysis. All depressed subjects started pharmacological treatment for depression shortly after a baseline magnetic resonance imaging (MRI) scan. At 12 weeks, patients underwent a follow-up MRI scan, and were categorized as either treatment remitters (n=23) or non-remitters (n=24). Among all patients, there was as a significant increase in WMHs over 12 weeks (t(46)=2.36, P=0.02). When patients were stratified by remission status, non-remitters demonstrated a significant increase in WMHs (t(23)=2.17, P=0.04), but this was not observed in remitters (t(22)=1.09, P=0.29). Other markers of brain integrity were also investigated including whole brain gray matter volume, hippocampal volume, and fractional anisotropy. No significant differences were observed in any of these markers during treatment, including when patients were stratified based on remission status. These results add to existing literature showing the association between WMH accumulation and LLD treatment outcomes. Moreover, this is the first study to demonstrate similar findings over a short interval (ie 12 weeks), which corresponds to the typical length of an antidepressant trial. These findings serve to highlight the acute interplay of cerebrovascular ischemic disease and LLD.

How should residual symptoms be defined in depressed patients who have remitted?

Symptomatic remission has been defined as a complete or near-complete absence of symptoms. Just as the distinction between remitters and nonremitters among treatment responders has clinical significance, the distinction between a complete and near-complete absence of symptoms itself might be important. Recent studies have reported a high frequency of residual symptoms in patients who are presumably in remission, and this raises questions about how residual symptoms are defined. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we compared the prevalence of residual symptoms based on different cutoff scores on 2 self-report measures of depression and then determined the association between residual symptoms and indices of psychosocial morbidity. We administered the 17-item Hamilton Rating Scale for Depression to 274 psychiatric outpatients diagnosed as having DSM-IV major depressive disorder who were in ongoing treatment. The patients completed the Clinically Useful Depression Outcome Scale (CUDOS) and Quick Inventory of Depressive Symptomatology (QIDS) and measures of psychosocial functioning and quality of life. We examined the frequency of residual symptoms in the 142 patients scoring in the remission range on the Hamilton Rating Scale for Depression. For both the CUDOS and QIDS, the threshold to define symptom presence strongly impacted on the prevalence of residual symptoms. The association between residual symptoms, psychosocial functioning, and quality of life varied according to the threshold used to define the symptoms. On the QIDS, a cutoff of 1 was a more valid indicator of the presence of residual symptoms than a cutoff of 2, whereas on the CUDOS, we recommend a cutoff of 2 be used to indicate the presence of residual symptoms. Examination of the frequency of specific symptoms suggests that the choice of scale might impact on which residual symptoms are considered the most frequent in treatment remitters.

Dismantling multicomponent behavioral treatment for insomnia in older adults: a randomized controlled trial.

Recently, the use of multicomponent insomnia treatment has increased. This study compares the effect of single component and multicomponent behavioral treatments for insomnia in older adults after intervention and at 3 months and 1 yr posttreatment. A randomized, controlled study. Veterans Affairs medical center. 179 older adults (mean age, 68.9 yr ± 8.0; 115 women [64.2%]) with chronic primary insomnia. Participants were randomly assigned to 6 wk of stimulus control therapy (SCT), sleep restriction therapy (SRT), the 2 therapies combined into a multicomponent intervention (MCI), or a wait-list control group. Primary outcomes were subjective (daily sleep diary) and objective (actigraphy) measures of sleep-onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TIB), and sleep efficiency (SE). Secondary outcomes were clinical measures including response and remission rates. There were no differences between the single and multicomponent interventions on primary sleep outcomes measured by diary and actigraphy. All treatments produced significant improvement in diary-reported sleep in comparison with the control group. Effect sizes for sleep diary outcomes were medium to large. Treatment gains were maintained at follow-up for diary and actigraph measured SOL, WASO, and SE. The MCI group had the largest proportion of treatment remitters. For older adults with chronic primary insomnia, the findings provide initial evidence that SCT, SRT, and MCI are equally efficacious and produce sustainable treatment gains on diary, actigraphy, and clinical outcomes. From a clinical perspective, MCI may be a preferred treatment due to its higher remission rate. Behavioral Intervention for Insomnia in Older Adults. NCT01154023. URL: http://clinicaltrials.gov/ct2/show/NCT01154023?term=Behavioral+Intervention+for+Insomnia+in+Older+Adults&rank=1.

Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment

In order to test the hypotheses that pretreatment metabolic activity in the midbrain and the rostral anterior cingulate may predict remission in response to medications enhancing monoaminergic transmission, we compared relative regional cerebral metabolic rate of glucose (rCMRglu) using positron emission tomography (PET) in medication-free patients with major depression who remitted after 3 months of monoaminergic medication, with non-remitters on the same treatment. [ 18F]-FDG PET was conducted in a group of 33 drug-free DSM-IV major depression subjects prior to antidepressant treatment. Patients were prescribed paroxetine initially (61%) unless they had failed paroxetine previously. Treatment was then managed by the subjects' own physician with 91% receiving a selective serotonin reuptake inhibitor and 78% another non-selective monoamine reuptake inhibitor during the 3 months of treatment. Voxel-based parametric brain maps of remitters were compared with maps of non-remitters using SPM2. Remission was defined as a > 50% decrease in and a final score of ≤ 10 on the 24-item Hamilton Depression Rating Scale. We found that treatment remitters have lower activity in a single contiguous brain region (with global maxima in the midbrain, cluster level P = 0.013, corrected for multiple comparison (CMC)), prior to treatment, compared with non-remitters to 3 months of community-based monoaminergic antidepressant treatment. Degree of improvement correlated with pretreatment midbrain activity. Pretreatment clinical picture and intensity of treatment did not distinguish remitters. No other area of the brain showed a significant difference between remitters and non-remitters even with CMC completely disabled. Lower relative regional brain activity in the region of monoaminergic nuclei prior to treatment predicts remission in response to 3 months of antidepressant treatment, despite no clinical differences at baseline and no difference in treatment intensity. Brain imaging is a potential objective laboratory technique that may guide treatment selection where clinical methods have not shown promise. Prospective studies are needed to replicate these findings and determine whether outcome prediction is limited to a specific class of antidepressants.

Nonresponse, partial response, and failure to achieve remission: humanistic and cost burden in major depressive disorder

To characterize the spectrum of clinical outcomes achieved with depression treatment and the associated impact on quality of life (QOL), functional status, overall well-being, health-care costs, and productivity. Electronic databases including Medline were searched for English language sources between 1995 and 2007 using key words of depression, nonresponse, partial response, and remission and QOL, functional status, utility, cost, and productivity. Relevant abstracts were obtained for 488 references and full-text articles were reviewed that included primary data and compared outcomes by treatment response. Data were abstracted from 26 full-text articles. Detailed evidence tables were prepared with the relevant data as well as information on the study design. All data abstracted were checked for accuracy. synthesis: Treatment remitters and partial responders reported clinically and statistically significant improvements in QOL, functional status, and overall well-being compared to nonresponders. Annual health-care costs and productivity losses were significantly lower for remitters and partial responders compared to nonresponders. The reduced disease burden for remitters and partial responders compared to nonresponders indicates that new treatment strategies that improve the rates of response/remission with initial treatment might have value to patients and to society.

Heterogeneity among depressed outpatients considered to be in remission

More than a decade ago, a consensus panel recommended that remission be defined on the 17-item version of the Hamilton Rating Scale for Depression (HAM-D) as a cutoff of less than 7. Recently, some investigators have suggested that this threshold to define remission may be too high. If true, this means that heterogeneity exists within the group of treatment remitters accounting for variance in psychosocial function and relapse risk. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined whether there is heterogeneity within the group of patients that are typically classified as remitters. Three hundred three depressed psychiatric outpatients were rated on the Standardized Clinical Outcome Rating for Depression, an index of Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition remission status, and the 17-item HAM-D. Approximately half of the patients completed a measure of psychosocial impairment. Treatment responders were divided into 2 groups, remitters (HAM-D ≤7) and nonremitters (HAM-D ≥8). The treatment remitters were further subdivided into 2 groups, remitters with and without mild residual symptoms (HAM-D 3-7 vs 0-2). We refer to these 3 nonoverlapping groups as responders, partial remitters (ie, remitters with mild residual symptoms), and full remitters (remitters without residual symptoms). Responders scored statistically significantly higher, indicating greater psychosocial impairment, than the entire group of remitters, and the partial remitters scored significantly higher than the full remitters. Among the responders, the correlation between remission status and functioning was −.49 ( P < .01). Among the remitters, the correlation between residual symptom status and functioning was nearly as high (−.42, P < .05). These results suggest that there is as much heterogeneity among patients who are typically considered to be in remission as there is among responders. This supports recommendations to lower the cutoff on the HAM-D to define remission.

Neurochemical Effects of Olanzapine in First-Hospitalization Manic Adolescents: A Proton Magnetic Resonance Spectroscopy Study

We used proton magnetic resonance spectroscopy (1H MRS) to compare the in vivo effects of olanzapine on prefrontal N-acetyl-aspartate (NAA) levels in treatment remitters and nonremitters. Secondary aims of this study were to identify neurochemical predictors of successful olanzapine treatment and other neurochemical effects of olanzapine. In all, 20 adolescents admitted for their first hospitalization for bipolar disorder, type I, manic or mixed and 10 demographically matched healthy subjects were recruited. Manic adolescents were treated with olanzapine monotherapy and scanned at three time points (N = 19). Medial and left and right lateral ventral prefrontal NAA, choline, creatine/phosphocreatine, myo-inositol, and glutamate/glutamine were measured at baseline, prior to receiving medication, and on days 7 and 28 of treatment. Healthy subjects did not receive medication but underwent 1H MRS scans at the same time points to assess for normal variability in metabolites over time. Although there was no overall increase in NAA in manic adolescents following 28 days of treatment with olanzapine, olanzapine remitters (N = 11, 58%) exhibited a greater increase in medial ventral prefrontal NAA compared with nonremitters (N = 8, 42%, p = 0.006). Specifically, from baseline to end point, NAA levels decreased in nonremitters (p = 0.03) and increased in remitters (p = 0.05). Manic adolescents treated with olanzapine had an increase from baseline to day 7 in medial (p = 0.002) and right lateral (p = 0.02) ventral prefrontal choline. Baseline medial ventral prefrontal choline was greater in olanzapine remitters than in nonremitters (p = 0.001). Successful treatment of mania with olanzapine may lead to increased ventral prefrontal neuronal viability and/or function as compared to unsuccessful treatment with olanzapine. Additionally, olanzapine-induced increases in choline may lead to alteration of abnormalities in cell membrane metabolism or second messenger pathways that are thought to be involved in the pathophysiology of bipolar disorder.

No brain perfusion impairment at long-term follow-up in elderly patients treated with electroconvulsive therapy for major depression.

No functional neuroimaging study has previously assessed the long-term effects of electroconvulsive therapy (ECT) on brain perfusion. In this study, long-term follow-up brain perfusion in elderly patients treated with ECT for severe unipolar major depression was assessed. In 14 elderly major depressed patients who were ECT remitters, 22 elderly major depressed patients who were pharmacological treatment remitters and 25 age- and sex-matched healthy controls, a medication-free brain 9mTc-HMPAO-SPECT was performed after a minimum period of 12 months of euthymia and, in the case of the ECT remitters, at least 12 months after the last ECT session. Brain perfusion ratios in major depressed patients administered ECT were similar to those in major depressed patients receiving pharmacological treatment and in control subjects. This result suggests that elderly patients given ECT for severe unipolar major depression do not suffer brain perfusion abnormalities at long-term follow-up. Our study adds new evidence in favor of the safety of the ECT, particularly in elderly subjects.

Prospective assessment of sexual function in women treated for recurrent major depression

Although multiple factors may influence the sexual function of depressed women over the course of treatment, the independent contributions of these factors are poorly understood. The current study examined the effects of depression, SSRI treatment, and sexual partner availability on women's sexual function. The sexual function of 68 recurrently depressed women was assessed at 3-month intervals over a 1-year course of treatment with interpersonal psychotherapy with or without adjunctive SSRI treatment. Random regression models assessing changes in sexual function were conducted to test the effects of three time-dependent covariates: depression symptom scores, sexual partner availability, and SSRI medication status. Controlling for the other variables, depressive symptoms were associated with decrements in sexual desire, sexual cognition/fantasy, sexual arousal, orgasmic function, and global evaluations of sexual function. SSRI treatment was associated with orgasmic difficulty only. The availability of a sexual partner was associated with increased sexual arousal, orgasmic function, and sexual behavior. Among treatment remitters, patient reports of severe sexual dysfunction did not change over the course of treatment, although mild improvement was observed in patients' global assessment of the quality of their sexual function. This report illustrates the prevalence and persistence of sexual dysfunction in this sample, and highlights the importance of monitoring both pharmacologic and psychosocial variables that can affect the sexual function of recurrently depressed women throughout the course of treatment.