Exercise elevates serum brain-derived neurotrophic factor in partially remitted depression.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine implicated in the pathogenesis of major depressive disorder (MDD). In MDD, serum BDNF levels are attenuated. Healthy adults show BDNF elevation after exercise. To investigate activity-dependent BDNF elevation in MDD, thirty-seven participants with partially remitted MDD were allocated to either a bout of strenuous or light activity. Serum was collected before and after the intervention. BDNF was measured using a highly sensitive and specific enzyme-linked immunosorbent assay. Significant BDNF elevation in the strenuous activity group emerged. This study confirms exercise-dependent serum BDNF elevation in MDD. Preregistration: German Clinical Trials Register (DRKS0001515).

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.

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.

Neurocognitive performance in patients with depression compared to healthy controls: Association of clinical variables and remission state.

Cognitive impairment in Major Depressive Disorder (MDD) has been postulated to persist into remission. However, inconsistent definitions of clinical remission, patterns and influencing factors, isolated cognitive tasks, and the lack of appropriately matched controls (HCs) present significant limitations of previous studies. Furthermore, studies investigating cognition in partially remitted patients are particularly scarce. This study compares the cognition of MDD patients (N = 65) and HCs (N = 65), matched by one-to-one recruitment strategy for age, sex, and education (ages 19-60). The neuropsychological (NPS) performance was measured via an extensive NPS-test battery and analysed retrospectively, accounting for demographic and clinical variables. Full remission was defined as HAMD cut off ≤7, partial remission as HAMD 8-18. The findings show entire MDD group and partially remitted MDD with significantly poorer NPS performance compared to HCs, while remitted MDD patients did not differ significantly from HCs. This underscores how critical a clear definition of remission is to compare studies on MDD. The clinical variable 'number of hospitalizations' had a significant effect on cognition, whereas current symptom severity did not correlate with performance on any cognitive domain. Higher number of hospitalizations may be associated with higher burden of illness and greater neurobiological "scar effects".

Serum calcium levels and neuropsychological performance in depression and matched healthy controls: Reversal of correlation a marker of the aging cognitive clock?

BACKGROUND: Major depressive disorder (MDD) is associated with cognitive impairment, that might be related to disturbed calcium homeostasis. Calcium-related processes have also been implicated in age related cognitive decline. Since serum calcium and brain interstitial fluids maintain long-term equilibrium under normal physiological states, serum calcium levels could affect neuronal and hence cognitive function. High serum calcium has been associated with cognitive decline in geriatric populations, whereas evidence for MDD and healthy populations is less consistent. METHODS: Differences in neuropsychological (NPS) performance and their relationship with serum calcium (total, ionized, total to ionized ratio) in (partially) remitted MDD patients (n = 59) and healthy controls (HC) (n = 59) individually matched for age, gender and education (age-range 19-60 years) were examined. Modulation of study parameters and their interaction by the factor age was investigated, with subgroups young and old divided at median = 37 years. Participants provided blood samples and completed an extensive NPS test battery. RESULTS: MDD showed significantly poorer NPS performance compared to HC. Serum calcium associated positively with NPS performance in HC and negatively in MDD for entire age-range samples. While younger MDD and HC showed positive NPS-calcium correlations, older MDD and HC exhibited negative NPS-calcium correlations ('correlation reversal'). Age had a significant effect on cognition and ionized calcium and interacted with illness-status, with an exaggerated influence on cognition in MDD compared to HC. CONCLUSIONS: The results place calcium 'correlation reversal' to early middle-age time window, which may be accelerated for MDD and highlight the central role of calcium pathways in normal and pathological cognitive aging.