Effectiveness of Schema Therapy versus Cognitive Behavioral Therapy versus Supportive Therapy for Depression in Inpatient and Day Clinic Settings: A Randomized Clinical Trial.

INTRODUCTION: Schema therapy (ST) reduces depressive symptoms, but clinical trials have not investigated its effectiveness for patients suffering from severe forms of depression and high rates of comorbidities. There is high demand for exploring and improving treatments for this patient group. The objective of the current study was to evaluate whether ST is more effective than individual supportive therapy (IST) and noninferior compared with cognitive behavioral therapy (CBT) in treating depression. METHODS: For this clinical trial, medicated patients were recruited in inpatient and day clinic settings. The major inclusion criteria were age between 18 and 75 years and primary diagnosis of depression without psychotic symptoms. A total of 292 participants were randomized to ST, CBT, or IST and received 7 weeks of psychotherapy (up to 14 individual and 14 group sessions). The primary outcome was change in depression severity after treatment measured by Beck Depression Inventory-II. Primary test for efficacy was superiority of ST over IST. Secondary test was noninferiority of ST compared with CBT. Multilevel modeling was conducted. The results at 6-month follow-up were explored. RESULTS: Across treatment, ST was not superior to IST. Secondary outcome analyses and completer analyses showed similar results. However, ST showed clinically relevant noninferiority compared with CBT. CONCLUSION: ST for depression as part of a psychiatric care program showed clinical noninferiority compared to CBT, without being superior to IST. ST represents a potentially useful addition to the therapeutic repertoire for the treatment of depression but its efficacy, including long-term efficacy, should be evaluated further.

Evaluating the role of maladaptive personality traits in schema therapy and cognitive behavioural therapy for depression.

BACKGROUND: Advancements in the treatment of depression are pivotal due to high levels of non-response and relapse. This study evaluated the role of personality pathology in the treatment of depression by testing whether maladaptive personality traits (1) predict changes in depression over treatment or vice versa, (2) change themselves over treatment, (3) change differentially depending on treatment with schema therapy (ST) or cognitive behavioural therapy (CBT), and (4) moderate the effectiveness of these treatments. METHODS: We included 193 depressed inpatients (53.4% women, Mage = 42.9, SD = 13.4) participating in an assessor-blind randomized clinical trial and receiving a 7-week course of ST or CBT. The research questions were addressed using multiple indicator latent change score models as well as multigroup structural equation models implemented in EffectLiteR. RESULTS: Maladaptive traits did not predict changes in depressive symptoms at post-treatment, or vice versa. However, maladaptive trait domains decreased over treatment (standardized Δµ range: -0.38 to -0.89), irrespective of treatment with ST or CBT. Maladaptive traits at baseline did not moderate the effectiveness of these treatments. CONCLUSIONS: Self-reported maladaptive personality traits can change during treatment of depression, but may have limited prognostic or prescriptive value, at least in the context of ST or CBT. These results need to be replicated using follow-up data, larger and more diverse samples, and informant-rated measures of personality pathology.

Schema therapy versus cognitive behavioral therapy versus individual supportive therapy for depression in an inpatient and day clinic setting: study protocol of the OPTIMA-RCT.

BACKGROUND: Major depressive disorder represents (MDD) a major cause of disability and disease burden. Beside antidepressant medication, psychotherapy is a key approach of treatment. Schema therapy has been shown to be effective in the treatment of psychiatric disorders, especially personality disorders, in a variety of settings and patient groups. Nevertheless, there is no evidence on its effectiveness for MDD in an inpatient nor day clinic setting and little is known about the factors that drive treatment response in such a target group. METHODS: In the current protocol, we outline OPTIMA (OPtimized Treatment Identification at the MAx Planck Institute): a single-center randomized controlled trial of schema therapy as a treatment approach for MDD in an inpatient and day clinic setting. Over the course of 7 weeks, we compare schema therapy with cognitive behavioral therapy and individual supportive therapy, conducted in individual and group sessions and with no restrictions regarding concurrent antidepressant medication, thus approximating real-life treatment conditions. N = 300 depressed patients are included. All study therapists undergo a specific training and supervision and therapy adherence is assessed. Primary outcome is depressive symptom severity as self-assessment (Beck Depression Inventory-II) and secondary outcomes are clinical ratings of MDD (Montgomery-Asberg Depression Rating Scale), recovery rates after 7 weeks according to the Munich-Composite International Diagnostic Interview, general psychopathology (Brief Symptom Inventory), global functioning (World Health Organization Disability Assessment Schedule), and clinical parameters such as dropout rates. Further parameters on a behavioral, cognitive, psychophysiological, and biological level are measured before, during and after treatment and in 2 follow-up assessments after 6 and 24 months after end of treatment. DISCUSSION: To our knowledge, the OPTIMA-Trial is the first to investigate the effectiveness of schema therapy as a treatment approach of MDD, to investigate mechanisms of change, and explore predictors of treatment response in an inpatient and day clinic setting by using such a wide range of parameters. Insights from OPTIMA will allow more integrative approaches of psychotherapy of MDD. Especially, the identification of intervention-specific markers of treatment response can improve evidence-based clinical decision for individualizing treatment. TRIAL REGISTRATION: Identifier on clinicaltrials.gov : NCT03287362 ; September, 12, 2017.

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.

MicroRNA-9 controls dendritic development by targeting REST.

MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth.

The optogenetic (r)evolution.

Optogenetics is a rapidly evolving field of technology that allows optical control of genetically targeted biological systems at high temporal and spatial resolution. By heterologous expression of light-sensitive microbial membrane proteins, opsins, cell type-specific depolarization or silencing can be optically induced on a millisecond time scale. What started in a petri dish is applicable today to more complex systems, ranging from the dissection of brain circuitries in vitro to behavioral analyses in freely moving animals. Persistent technical improvement has focused on the identification of new opsins, suitable for optogenetic purposes and genetic engineering of existing ones. Optical stimulation can be combined with various readouts defined by the desired resolution of the experimental setup. Although recent developments in optogenetics have largely focused on neuroscience it has lately been extended to other targets, including stem cell research and regenerative medicine. Further development of optogenetic approaches will not only highly increase our insight into health and disease states but might also pave the way for a future use in therapeutic applications.