Insight and Outcome in Long-Term Psychotherapies of Depression.

Objectives: In different therapeutic approaches, insight is acknowledged as an important part of patient's therapeutic change process. We examined whether the level of insight (1) differs between psychoanalytic (PA), psychodynamic (PD) and cognitive-behavioral therapy (CBT), and (2) predicts long-term symptomatic outcome. Methods: A completer sample of 67 depressed patients from the Munich Psychotherapy Study was analyzed. Symptoms were assessed with Beck Depression Inventory (BDI) and Symptom Checklist-Revised (SCL-90-R) at pre-treatment and three-year follow-up. Insight was assessed from 242 sessions of mid-therapy phase with the Experiencing Scale. Results: The general level of insight was higher in PA as compared to CBT, and associated with lower depressive symptoms (BDI) across all three therapeutic modalities at three-year follow-up. Insight was unrelated to general distress (SCL-90-R). Exploratory analyses suggested that patients treated with PA showed higher levels of insight especially in high quality sessions (assessed by therapist). Patients for whom the extent of insight was positively linked to session quality, suffered from more depressive symptoms at three-year follow-up than patients gaining insight when session quality was low. Conclusion: Insight differs between PA and CBT and may be a common change mechanism in long-term psychotherapies.

Replicability of motor cortex-excitability modulation by intermittent theta burst stimulation.

OBJECTIVE: Transcranial Magnetic Stimulation (TMS) allows for cortical-excitability (CE) assessment and its modulation has been associated with neuroplasticity-like phenomena, thought to be impaired in neuropsychiatric disorders. However, the stability of these measures has been challenged, defying their potential as biomarkers. This study aimed to test the temporal stability of cortical-excitability modulation and study the impact of individual and methodological factors in determining within- and between-subject variability. METHODS: We recruited healthy-subjects to assess motor cortex (MC) excitability modulation, collecting motor evoked potentials (MEP) from both hemispheres, before and after left-sided intermittent theta burst stimulation (iTBS), to obtain a measure of MEPs change (delta-MEPs). To assess stability across-time, the protocol was repeated after 6 weeks. Socio-demographic and psychological variables were collected to test association with delta-MEPs. RESULTS: We found modulatory effects on left MC and not on right hemisphere following iTBS of left MC. Left delta-MEP was stable across-time when performed immediately after iTBS (ICC = 0.69), only when obtained first in left hemisphere. We discovered similar results in a replication cohort testing only left MC (ICC = 0.68). No meaningful associations were found between demographic and psychological factors and delta-MEPs. CONCLUSIONS: Delta-MEP is stable immediately after modulation and not impacted by different individual factors, including expectation about TMS-effect. SIGNIFICANCE: Motor cortex excitability modulation immediately after iTBS should be further explored as a potential biomarker for neuropsychiatric diseases.

Hemispheric asymmetry of motor cortex excitability in mood disorders - Evidence from a systematic review and meta-analysis.

OBJECTIVE: Mood disorders have been associated with lateralized brain dysfunction, on the left-side for depression and right-side for mania. Consistently, asymmetry of cortical excitability, as measured by transcranial magnetic stimulation (TMS) has been reported. Here, we reviewed and summarized work assessing such measures bilaterally in mood disorders. METHODS: We performed a systematic review and extracted data to perform meta-analyses of interhemispheric asymmetry of motor cortex excitability, assessed with TMS, across different mood disorders and in healthy subjects. Additionally, potential predictors of interhemispheric asymmetry were explored. RESULTS: Asymmetry of resting motor threshold (MT) among healthy volunteers was significant, favoring lower right relative to left-hemisphere excitability. MT was also significantly asymmetric in major depressive disorder (MDD), but with lower excitability of the left -hemisphere, when compared to the right, no longer observed in recovered patients. Findings on intracortical facilitation were similar. The few trials including bipolar depression revealed similar trends for imbalance, but with lower right hemisphere excitability, relative to the left. CONCLUSIONS: There is interhemispheric asymmetry of motor cortical excitability in MDD, with lower excitability on left when compared to right-side. Interhemispheric asymmetry, with lower right relative to left-sided excitability, was found for bipolar depression and was also suggested for healthy volunteers, in a pattern that is clearly distinct from MDD. SIGNIFICANCE: Mood disorders display asymmetric motor cortical excitability that is distinct from that found in healthy volunteers, supporting the presence of lateralized brain dysfunction in these disorders.

Day-to-day variability in motor threshold during rTMS treatment for depression: Clinical implications.

BACKGROUND: When repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration. OBJECTIVE: Here, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity. METHODS: We conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily. RESULTS: For each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved. CONCLUSIONS: In conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.

Reducing motor evoked potential amplitude variability through normalization.

Background: Transcranial Magnetic Stimulation (TMS) is used for in vivo assessment of human motor cortical excitability, with application of TMS pulses over the motor cortex resulting in muscle responses that can be recorded with electromyography (EMG) as Motor Evoked Potentials (MEPs). These have been widely explored as potential biomarkers for neuropsychiatric disorders but methodological heterogeneity in acquisition, and inherent high variability, have led to constraints in reproducibility. Normalization, consisting in scaling the signal of interest to a known and repeatable measurement, reduces variability and is standard practice for between-subject comparisons of EMG. The effect of normalization on variability of MEP amplitude has not yet been explored and was assessed here using several methods. Methods: Three maximal voluntary isometric contractions (MVICs) and 40 MEPs were collected from the right hand in healthy volunteers, with a retest session conducted 4 to 8 weeks later. MEP amplitude was normalized using either external references (MVICs) or internal references (extreme MEPs). Iterative re-sampling of 30 normalized MEPs per subject was repeated 5,000 times to define, for each normalization method, distributions for between-subject coefficients of variation (CV) of the mean MEP amplitude. Intra-class correlation coefficients (ICC) were used to assess the impact of normalization on test­retest stability of MEP amplitude measurements. Results: In the absence of normalization, MEPs collected from the right hand of 47 healthy volunteers were within reported values regarding between-subject variability (95% confidence intervals for the CV: [1.0567,1.0577]) and showed good temporal stability (ICC = 0.77). Internal reference normalization substantially reduced between-subject variability, by values of up to 64%, while external reference normalization had no impact or increased between-subject variability. Normalization with the smallest references reduced test­retest stability, with use of the largest references resulting in slight reduction or improvement of ICCs. Internal reference normalization using the largest MEPs was found to be robust to several sensitivity analyses. Conclusion: Internal, but not external, reference normalization reduces between-subject variability of MEP amplitude, and has a minimal impact on within-subject variability when conducted with the largest references. Additional research is necessary to further validate these normalization methods toward potential use of MEPs as biomarkers of neuropsychiatric disorders.

Treinamento via internet em pesquisa clínica: uma experiência com o psychotherapy process Q-Set (PQS) / Internet-based clinical research training: an experience with the psychotherapy process Q-Set (PQS)

INTRODUÇÃO: Nas últimas décadas, os estudos dos processos das psicoterapias aumentaram significativamente nosso conhecimento sobre os mecanismos de ação subjacentes ao encontro terapêutico. Entre os vários instrumentos e métodos para avaliar o processo terapêutico, destacamos o Psychotherapy Process Q-Set1. O PQS compreende 100 itens que descrevem as características do paciente, do terapeuta e da sua interação, podendo ser aplicado para descrever o processo de uma única terapia ou de um grupo de terapias. O uso de PQS requer treinamento intensivo. Idealmente, o aluno deve discutir as dificuldades e dúvidas com outros avaliadores experientes, a fim de esclarecer o seu uso e clarificar os significados sutis. Esta breve comunicação descreve um treinamento baseado na internet e o processo de aprendizagem de duas pesquisadoras com diferentes níveis de experiência com o PQS. RESULTADOS e DISCUSSÃO: O progresso do treinamento, baseado em valores de confiabilidade (correlação de Pearson) entre o avaliador sênior e as pesquisadoras demonstra que o treinamento via internet pode ser uma alternativa para pesquisadores localizados longe dos grandes centros de pesquisa em psicoterapia. Esse tipo de treinamento em investigação é suscetível de ser replicado com sucesso em outros grupos e, possivelmente, com outros métodos de pesquisa em psicoterapia.(AU)

INTRODUCTION: In recent decades, psychotherapy process studies have been adding significantly to our knowledge about the mechanisms of action underlying the therapeutic encounter. Among the various instruments and methods developed to assess the therapeutic process, we highlight the Psychotherapy Process Q-set1. The PQS comprises 100 items that describe characteristics of the patient, therapist and their interaction and may be applied to describe either the process of a single therapy or a group of therapies. The use of PQS requires intense training. Ideally, the learner should have the opportunity to discuss difficulties and doubts with other experienced raters in order to clarify its use and subtle meanings. This brief communication aims to describe an internet-based training and the learning process of two PQS trainees with different levels of experience. RESULTS and DISCUSSION: The training progression, based on reliability values (Pearson correlation) between senior rater/teacher and both trainees demonstrates that the PQS internet-based training through internet communication can be a promising alternative for researchers who are located far from major centers of psychotherapy research. This kind of research training is likely to be successfully replicated in other groups and possibly with other psychotherapy research methods.(AU)