Cognitive remediation therapy for partially remitted unipolar depression: A single-blind randomized controlled trial.

BACKGROUND: There is an urgent need for the development and evaluation of targeted interventions for cognitive impairment (CI) in patients with (partially) remitted major depressive disorder (MDD). The aim of our study was therefore to evaluate the effect of cognitive remediation therapy (CRT) on cognitive and psychosocial functioning in a sample of patients with MDD, taking into account comorbidity, psychopathology, remission status and CI profile. Furthermore, we compared a generalized training (GT) with an individualized training (IT) approach regarding their effects on cognition. METHODS: Sixty-two MDD patients in partial remission with CI were randomly assigned to a control group (CG), IT or GT. Participants of GT trained six cognitive subdomains (divided attention, selective attention, alertness, working memory, planning and response inhibition), whereas participants of IT trained their three most deficient cognitive subdomains as identified at baseline. Participants of both intervention groups trained three times per week over a five-week period. Both training groups received additional 30-minute compensatory-transfer sessions once per week. RESULTS: Attention appeared to be the most frequently impaired cognitive domain as well as the domain which was significantly improved by CRT, with medium to large effect sizes. No difference in improvement was found between IT and GT. The analyses also revealed greater improvement in self-assessed psychosocial functioning in training participants (GT and IT combined) compared to the CG. LIMITATIONS: Due to the small sample size, the present results are preliminary in nature. CONCLUSION: CRT was well accepted, and patients transferred the attentional improvement to real life, as measured by self-assessed psychosocial functioning. IT yielded no additional advantages over GT. We propose CRT as an integral part of the treatment plan for patients with depression suffering from CI.

Abnormal Cerebellar Volume in Patients with Remitted Major Depression with Persistent Cognitive Deficits.

Cerebellar involvement in major depressive disorder (MDD) has been demonstrated by a growing number of studies, but it is unknown whether cognitive functioning in depressed individuals is related to cerebellar gray matter volume (GMV) abnormalities. Impaired attention and executive dysfunction are characteristic cognitive deficits in MDD, and critically, they often persist despite remission of mood symptoms. In this study, we investigated cerebellar GMV in patients with remitted MDD (rMDD) that showed persistent cognitive impairment. We applied cerebellum-optimized voxel-based morphometry in 37 patients with rMDD and with cognitive deficits, in 12 patients with rMDD and without cognitive deficits, and in 36 healthy controls (HC). Compared with HC, rMDD patients with cognitive deficits had lower GMV in left area VIIA, crus II, and in vermal area VIIB. In patients with rMDD, regression analyses demonstrated significant associations between GMV reductions in both regions and impaired attention and executive dysfunction. Compared with HC, patients without cognitive deficits showed increased GMV in bilateral area VIIIB. This study supports cerebellar contributions to the cognitive dimension of MDD. The data also point towards cerebellar area VII as a potential target for non-invasive brain stimulation to treat cognitive deficits related to MDD.

Cognitive remediation therapy modulates intrinsic neural activity in patients with major depression.

BACKGROUND: Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial. METHODS: In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS). RESULTS: MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance. CONCLUSIONS: Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Predictors of cognitive remediation therapy improvement in (partially) remitted unipolar depression.

BACKGROUND: There is urgent need for development and evaluation of targeted interventions for cognitive deficits in (partially) remitted major depression. Until now the analyses of the moderators of treatment efficacy were only examined in mixed samples of patients with schizophrenia, affective spectrum and schizoaffective disorders. Thus, the aim of our study was to evaluate the predictors of cognitive remediation therapy (CRT) improvement in a sample of (partially) remitted major depressive disorder patients. METHODS: Reliable Change Index with corrections for practice effects was calculated for each participant as an indicator for training improvement. Thirty eight patients, who were randomized within our previously conducted CRT clinical trial, were divided into "Improvers" and "Nonimprovers" in the attention domain, to compare them on sociodemographic, psychopathological, neurocognitive, psychosocial and training factors. RESULTS: We detected 13 training participants who improved reliably in the attention domain. Illness duration was the only factor which significantly differentiated between Improvers and Nonimprovers. No significant differences between Improvers and Nonimprovers in terms of other clinical variables, sociodemographic and neuropsychological factors were found. LIMITATIONS: Exploratory research results should be taken with caution. Focus on the attention domain could have led to a limited point of view. CONCLUSION: Our findings represent a first analysis of the predictors of cognitive remediation training improvement in (partially) remitted unipolar depression. Much more work should be done to refine cognitive treatment approaches. An initiation of cognitive training in early stages of the disease could be beneficial for the affected patients.

Cognitive Impairment Along the Course of Depression: Non-Pharmacological Treatment Options.

Major Depressive Disorder (MDD) is one of the most common psychiatric disorders, with a large global impact on both the individual and the society. In this narrative review, we summarize neurocognitive deficits during acute and (partially) remitted states of depression. Furthermore, we outline the potential negative effect of cognitive impairment (CI) on functional recovery, and discuss the role of several variables in the development of CI for MDD patients. Though there is cumulating evidence regarding persistent CI in unipolar depression, research on treatment options specific for this patient group is still scarce. Hence the central aim of our review is to present non-pharmacological interventions, which are thought to reduce CI in affected MDD patients. We discuss cognitive remediation therapy (CRT), physical exercise, yoga, mindfulness-based therapy, and modern neuromodulation approaches like neurostimulation and neurofeedback training. In conclusion, we propose future directions for research on CI in depression. Looking further ahead, we suggest creative interventional designs that include a direct comparison of different non-pharmacological treatment approaches on neurocognition and functional outcome of MDD. Furthermore, additive and synergistic effects of CRT with other treatment approaches should be examined and compared to create multimodal and even personalized intervention programs.