Neural predictors of successful brief psychodynamic psychotherapy for persistent depression (original) (raw)
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Psychiatry Research: Neuroimaging, 2018
Longitudinal neuroimaging studies in major depression have revealed cortico-limbic abnormalities which are modulated by treatment. We performed a systematic review and metaanalysis of psychotherapy treatment studies measuring neural function and metabolism using fMRI, PET, SPECT and MRS. Seventeen studies were included in the systematic review, total of 200 major depression participants (mean age 37.6 years), all medication free, and 116 healthy controls (mean age 36.4 years). Neuroimaging assessments were performed prior to initiation of treatment and following course of treatment. Treatment durations were: 16-30 weeks for CBT, 11 weeks for behavioral activation therapy, and up to 15 months for psychodynamic psychotherapy. The meta-analysis consisted of studies in which both groups had same serial scans and comparable tasks; total of 5 studies with visual presentation tasks of emotional stimuli: 55 patients (mean age: 38.7 years) and 55 healthy controls (mean age: 36.3 years). The meta-analysis revealed a significant group by time effect in left rostral anterior cingulate, in which patients showed increased activity following psychotherapy while healthy controls showed a decrease at follow up. Longitudinal treatment effects revealed reduced left precentral cortical activity in major depression. Findings could be indicative of improvements in emotion responsivity that may be achieved following psychotherapy.
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. [ 18 F]-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 N 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.
EPA-0142 – Neural changes in depressed patients during psychodynamic psychotherapy: An fMRI Study
European Psychiatry, 2014
Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N=16) and control participants matched for sex, age, and education (N=17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.
Psychology, 2012
Major depressive disorder (MDD) is a syndrome, which is quite frequent in the society, can be recurrent and shows symptoms of emotional, cognitive and behavioral disorder. Brain imaging studies support that patients diagnosed with MDD suffer dysfunction in limbic structures such as frontal cortex, amygdala, hippocampus and cingulate cortex and basal ganglions that regulate these functions. Psychotherapy is an effective treatment option for prevention of recurrent depressive attacks as well as for acute treatment of depression. It is thought that psychotherapy shows its effect by focusing on misleading cognitions and emotional information processing processes that lead to rise and persistence of symptoms of depression, which in turn boosts problem solving and coping skills. Neurobiological reflections of clinical recovery achieved by psychotherapy are not yet well known. In this study, it is aimed to review cognitive behavioral psychotherapy (CBT), interpersonal psychotherapy (IPT) and psychodynamic psychotherapy methods used frequently in treatment of MDD, along with functional brain imaging studies performed on treated depressive patients. Studies show that CBT lead to changes in the prefrontal cortex, cingulate cortex and amygdala metabolisms and activities. Activity of the subgenual cingulate cortex, which takes part in the regulation of the limbic activity, seems to play an important role in the response to CBT like in the response to antidepressant treatment. It was found that interpersonal psychotherapy (IPT) ensures recovery of metabolism and blood flow in the prefrontal cortex, cingulate cortex and basal ganglions. It was observed that psychodynamic therapy ensured recovery of abnormal activities in especially the prefrontal cortex and cingulate cortex in MDD, similar to the CBT and IPT. There is need for more long-term, follow-up studies in this area.
CNS Spectrums, 2009
ABSTRACTIntroduction: High frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising strategy to treat depression, but not all patients show a positive outcome.Objective: In this open study, we evaluate whether a favorable HF-rTMS treatment outcome could be predicted by baseline prefrontal brain glucose metabolism (CMRglc), measured by 18fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: A sample of 21 antidepressant-free, treatment-resistant depression (TRD) patients of the melancholic subtype received 10 sessions of HF-rTMS delivered on the left DLPFC. Patients underwent a static 18FDG-PET before and after HF-rTMS treatment.Results: Forty-three percent of the patients showed a reduction of at least 50% on their Hamilton Rating Scale for Depression scores. Higher baseline metabolic activities in the DLPFC and the anterior cingulate cortex (ACC) were associated with better clinical outco...
European Neuropsychopharmacology, 2002
Neurophysiological studies of major depression performed using PET imaging have shown abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in multiple prefrontal cortical and limbic structures that have been more generally implicated in emotional processing. The current study investigated the effects of antidepressant drug treatment in these regions using PET measures of glucose metabolism. Subjects with primary MDD (n527) were imaged while unmedicated and depressed, and, of these, 20 were rescanned following chronic antidepressant drug treatment. Regional metabolism was compared between unmedicated depressives and controls and between the pre-and post-treatment conditions in regions-of-interest (ROI) where metabolism or flow had previously been shown to be abnormal in unmedicated depressives. At baseline, the mean metabolism was increased in the left and right lateral orbital cortex / ventrolateral prefrontal cortex (PFC), left amygdala, and posterior cingulate cortex, and decreased in the subgenual ACC and dorsal medial / dorsal anterolateral PFC in the unmedicated depressives relative to controls, consistent with the results of previous studies. Following treatment, metabolism significantly decreased in the left amygdala and left subgenual ACC, and corresponding changes in the orbital and posterior cingulate cortices approached significance. The metabolic reduction in the amygdala and right subgenual ACC appeared largely limited to those subjects who both responded to treatment and remained well at 6 months follow-up, in whom the reduction in amygdala metabolism tightly correlated with the reduction in HDRS scores. The magnitude of the treatment-associated, metabolic change in the amygdala also correlated positively with the change in the stressed plasma cortisol levels measured during scanning. These data converge with those from other PET studies to indicate that primary MDD is associated with abnormal metabolism in limbic and paralimbic structures of the mesiotemporal and prefrontal cortices. Chronic antidepressant drug treatment reduces metabolism in the amygdala and ventral ACC in subjects showing a persistent, positive treatment response. In contrast, the persistence of the abnormal metabolic deficits in the dorsomedial / dorsal anterolateral PFC in MDD during treatment may conceivably relate to the histopathological changes reported in these regions in post mortem studies of MDD.
Acta Psychiatrica Scandinavica, 2000
Objective: To show that PET investigations of brain function in patients with major depression can contribute with valuable pathophysiological knowledge about brain function of these states. Methods: PET studies of cerebral blood¯ow or glucose metabolism in patients with unipolar or bipolar depression were reviewed. Results: The studies have great discrepancies related to sample size, subject selection, imaging protocol and image analysis. In spite of this shortcoming, there is evidence that patients with major depression have reduced blood¯ow and metabolism in the prefrontal cortex, particularly when they exhibit psychomotor retardation. Abnormalities are also found in the anterior cingulate gyrus and the basal ganglia. A few studies point to the possibility that response to antidepressant treatment can be predicted from PET scans. Conclusion: This evidence is consistent with the hypothesis that depressive symptoms are caused by dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia.
Brain Stimulation, 2015
Background: Although one of the most frequent diagnosed mental illnesses worldwide, it appears to be challenging to successfully treat major depressive disorder (MDD). Although the phenomenon of treatment-resistant depression (TRD) still remains unclear, the subgenual anterior cingulate cortex (sgACC) has been put forward as a possible neurobiological marker to evaluate clinical effects of a variety of antidepressant treatments, including repetitive transcranial magnetic stimulation (rTMS). Accelerated high-frequency (HF)-rTMS may have the potential to rapidly result in beneficial clinical outcomes in TRD. No studies yet examined the clinical effects of such accelerated stimulation treatment paradigms on sgACC regional glucose metabolism (CMRglc), nor the predictive value of the latter for clinical outcome. Objective: First, we investigated the predictive value of baseline sgACC metabolic activity for clinical outcome. Second, we hypothesized that in clinical responders only accelerated HF-rTMS treatment would result in significant metabolic decreases. Methods: We recruited right-handed antidepressant-free unipolar melancholic TRD patients to participate in a two-week randomized sham-controlled crossover HF-rTMS treatment study. Stimulation was applied to the left dorsolateral prefrontal cortex (DLPFC). Fifteen patients underwent 18FDG PET (CMRglc) at baseline (T0), after the first week (T1) of accelerated HF-rTMS and at the end of the treatment after the second week (T2). Results: Higher baseline sgACC metabolic activity may indicate beneficial clinical outcome to this kind of accelerated HF-rTMS treatment. Moreover, clinical response resulted in a significant decrease in sgACC CMRglc. Non-response did not affect sgACC CMRglc. Conclusions: Our results add to the sgACC as a specific neurobiological marker for anti-depressive response in accelerated HF-rTMS treatment paradigms. Such protocols may not only have the ability to result in fast clinical responses but they may also have potential to acutely modulate a dysfunctional sgACC.
Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder
2013
IMPORTANCE Currently, fewer than 40% of patients treated for major depressive disorder achieve remission with initial treatment. Identification of a biological marker that might improve these odds could have significant health and economic impact. OBJECTIVE To identify a candidate neuroimaging "treatment-specific biomarker" that predicts differential outcome to either medication or psychotherapy. DESIGN Brain glucose metabolism was measured with positron emission tomography prior to treatment randomization to either escitalopram oxalate or cognitive behavior therapy for 12 weeks. Patients who did not remit on completion of their phase 1 treatment were offered enrollment in phase 2 comprising an additional 12 weeks of treatment with combination escitalopram and cognitive behavior therapy. SETTING Mood and anxiety disorders research program at an academic medical center. PARTICIPANTS Men and women aged 18 to 60 years with currently untreated major depressive disorder. INTERVENTION Randomized assignment to 12 weeks of treatment with either escitalopram oxalate (10-20 mg/d) or 16 sessions of manual-based cognitive behavior therapy. MAIN OUTCOME AND MEASURE Remission, defined as a 17-item Hamilton Depression Rating Scale score of 7 or less at both weeks 10 and 12, as assessed by raters blinded to treatment. RESULTS Positive and negative predictors of remission were identified with a 2-way analysis of variance treatment (escitalopram or cognitive behavior therapy) × outcome (remission or nonresponse) interaction. Of 65 protocol completers, 38 patients with clear outcomes and usable positron emission tomography scans were included in the primary analysis: 12 remitters to cognitive behavior therapy, 11 remitters to escitalopram, 9 nonresponders to cognitive behavior therapy, and 6 nonresponders to escitalopram. Six limbic and cortical regions were identified, with the right anterior insula showing the most robust discriminant properties across groups (effect size = 1.43). Insula hypometabolism (relative to whole-brain mean) was associated with remission to cognitive behavior therapy and poor response to escitalopram, while insula hypermetabolism was associated with remission to escitalopram and poor response to cognitive behavior therapy. CONCLUSIONS AND RELEVANCE If verified with prospective testing, the insula metabolism-based treatment-specific biomarker defined in this study provides the first objective marker, to our knowledge, to guide initial treatment selection for depression. TRIAL REGISTRATION Registered at clinicaltrials.gov (NCT00367341)