You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Neural Responses to Sad Facial Expressions in Major Depression Following Cognitive Behavioral Therapy
Abstract 1:
BACKGROUND Affective facial processing is an important component of interpersonal relationships . The neural substrate has been examined following treatment with antidepressant medication but not with psychological therapies . The present study investigated the neural correlates of implicit processing of sad facial expressions in depression pretreatment and posttreatment with cognitive behavioral therapy ( CBT ) . METHODS The patient group consisted of 16 medication-free subjects ( mean age 40 years ) with a DSM-IV diagnosis of acute unipolar major depression , and the comparison group were 16 matched healthy volunteers . Subjects participated in a prospect i ve study with functional magnetic resonance imaging ( fMRI ) at weeks 0 and 16 . During the fMRI scans , subjects performed an affect recognition task with facial stimuli morphed to display varying intensities of sadness . Patients received 16 sessions of CBT . Functional magnetic resonance imaging data were analyzed for the mean activation and differential response to variable intensity ( load-response ) of facial affect processing . RESULTS During an acute depressive episode , patients showed elevated amygdala-hippocampal activity relative to healthy individuals . Baseline dorsal anterior cingulate activity in patients showed a significant relationship with subsequent clinical response . CONCLUSIONS These data provide further support for elevated amygdala activity in depression and suggest that anterior cingulate activity may be a predictor of treatment response to both pharmacotherapy and CBT


Title 2:
Neural correlates of emotional processing in depression: changes with cognitive behavioral therapy and predictors of treatment response.
Abstract 2:
Major depressive disorder ( MDD ) is characterized by the presence of disturbances in emotional processing . However , the neural correlates of these alterations , and how they may be affected by therapeutic interventions , remain unclear . The present study addressed these issues in a preliminary investigation using functional magnetic resonance imaging ( fMRI ) to examine neural responses to positive , negative , and neutral pictures in unmedicated MDD patients ( N = 22 ) versus controls ( N = 14 ) . After this initial scan , MDD patients were treated with cognitive behavioral therapy ( CBT ) and scanned again after treatment . Within regions that showed pre-treatment differences between patients and controls , we tested the association between pre-treatment activity and subsequent treatment response as well as activity changes from pre- to post-treatment . This study yielded three main findings . First , prior to treatment and relative to controls , patients exhibited overall reduced activity in the ventromedial prefrontal cortex ( PFC ) , diminished discrimination between emotional and neutral items in the amygdala , cau date , and hippocampus , and enhanced responses to negative versus positive stimuli in the left anterior temporal lobe ( ATL ) and right dorsolateral PFC . Second , CBT-related symptom improvement in MDD patients was predicted by increased activity at baseline in ventromedial PFC as well as the valence effects in the ATL and dorsolateral PFC . Third , from pre- to post-treatment , MDD patients exhibited overall increases in ventromedial PFC activation , enhanced arousal responses in the amygdala , cau date , and hippocampus , and a reversal of valence effects in the ATL . The study was limited by the relatively small sample that was able to complete both scan sessions , as well as an inability to determine the influence of comorbid disorders within the current sample . Nevertheless , components of the neural networks corresponding to emotion processing disturbances in MDD appear to resolve following treatment and are predictive of treatment response , possibly reflecting improvements in emotion regulation processes in response to CBT


Title 3:
Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings.
Abstract 3:
BACKGROUND Functional brain imaging studies in major depression have suggested abnormalities of areas , including the frontal cortex , cingulate gyrus , basal ganglia , and temporal cortex . We hypothesized that venlafaxine hydrochloride and interpersonal psychotherapy ( IPT ) might each alter brain blood flow in some or all of these areas on sequential single photon emission computed tomography ( SPECT ) scans . METHODS Twenty-eight men and women aged 30 to 53 years with a DSM-IV major depressive episode , a 17-item Hamilton Rating Scale for Depression ( HAM-D ) rating of 18 or higher , and antidepressant-naive for at least 6 months were studied . After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan , 1-T magnetic resonance imaging , and psychometric ratings , patients were assigned to different treatments . Thirteen patients had 1-hour weekly sessions of IPT from the same supervised therapist ( E.M. ) . Fifteen patients took 37.5 mg twice-daily of venlafaxine hydrochloride . Single-photon emission computed tomography scans and ratings were repeated at 6 weeks . RESULTS Both treatment groups improved substantially , more so with venlafaxine ( mean [ SD ] HAM-D scores at pretreatment : IPT , 22.7 [ 2.7 ] , and venlafaxine , 22.4 [ 3.1 ] ; and posttreatment : IPT , 16.2 [ 7.1 ] , and venlafaxine , 10.9 [ 8.6 ] ) . No patients had structural brain abnormalities . On analysis with statistical parametric mapping 96 , the venlafaxine group showed right posterior temporal and right basal ganglia activation ( P = .01 ) , while the IPT group had limbic right posterior cingulate and right basal ganglia activation ( P = .01 ) . CONCLUSIONS This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine , while both treatments demonstrated increased basal ganglia blood flow . This was , however , a short trial with a small sample , no control group , and different symptom reduction in the 2 groups


Title 4:
Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression.
Abstract 4:
BACKGROUND Pill-taking , expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder ( MDD ) . Aims To examine the effects of medication , placebo and supportive care on treatment outcome , and the relationships of expectations and therapeutic alliance to improvement . METHOD A total of 88 participants were r and omised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication .  Expectations of medication effectiveness , general treatment effectiveness and therapeutic alliance were measured ( trial registration at Clinical Trials.gov : NCT00200902 ) . RESULTS Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone . Therapeutic alliance predicted response to medication and placebo ; expectations of medication effectiveness at enrolment predicted only placebo response . CONCLUSIONS Pill treatment yielded better outcome than supportive care alone . Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment , suggesting that they were shaped by prior experiences outside the clinical trial


Title 5:
The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.
Abstract 5:
The relationship between therapeutic alliance and treatment outcome was examined for depressed out patients who received interpersonal psychotherapy , cognitive-behavior therapy , imipramine with clinical management , or placebo with clinical management .  Clinical raters scored videotapes of early , middle , and late therapy sessions for 225 cases ( 619 sessions ) . Outcome was assessed from patients ' and clinical evaluators ' perspectives and from depressive symptomatology . Therapeutic alliance was found to have a significant effect on clinical outcome for both psychotherapies and for active and placebo pharmacotherapy .  Ratings of patient contribution to the alliance were significantly related to treatment outcome ; ratings of therapist contribution to the alliance and outcome were not significantly linked . These results indicate that the therapeutic alliance is a common factor with significant influence on outcome


Title 6:
Change over time in brain serotonin transporter binding in major depression: effects of therapy measured with [(123) I]-ADAM SPECT.
Abstract 6:
Several studies have reported low brain serotonin transporter ( SERT ) binding in individuals with major depression . We hypothesized that the SERT st and ardized uptake ratio ( SUR ) values using [ ( 123 ) I]-ADAM single photon emission computed tomography would increase in depressed subjects who responded to cognitive behavior therapy ( CBT )  compared to CBT nonresponders . [ ( 123 ) I]-ADAM scans were acquired before and after 12 weeks of CBT from 20 depressed subjects and on two occasions 12 weeks apart from 10 nondepressed , healthy volunteers . The primary outcome measure was change over time in SUR values in the midbrain , medial temporal lobe , and basal ganglia regions . Depressed subjects demonstrated low pretreatment mean SUR values that significantly increased over time in the midbrain ( P = .011 ) , right medial temporal lobe ( P = .008 ) , and left medial temporal lobe ( P = .000 ) regions . Treatment responders showed a significant increase over time in SUR values in left medial temporal lobe ( P = .029 ) and right medial temporal lobe ( P = .007 ) regions . Partial and nonresponder subjects also showed a significant increase over time in SUR values in the left medial temporal region ( P = .040 ) ( vs. healthy volunteers ) , but to a lesser degree . The findings suggest that low pretreatment SERT binding may increase over time in some depressed individuals who experience symptom improvement
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 pre central cortical activity in major depression .
Findings could be indicative of improvements in emotion responsivity that may be achieved following psychotherapy