Effects of cognitive behavioural therapy on verbal learning and memory in major depression: Results of a randomized controlled trial.

Major depression (MD) is often accompanied by deficits in cognitive functioning. Cognitive behavioural therapy (CBT) has beneficial effects on MD. The aim of this study was to examine whether CBT affects verbal learning and memory in patients with MD and whether CBT that emphasizes exercise during behavioural activation has additional effects on verbal performance. Ninety-eight patients with MD were randomly assigned to CBT emphasizing either exercise during behavioural activation (CBT-E) or CBT emphasizing pleasurable low-energy activities (CBT-C). A passive waiting list control group was also involved (WL). Thirty nondepressed age- and sex-matched controls were included to examine potential verbal learning and memory alterations in MD at baseline. Neuropsychological measures were assessed at baseline and after 16 weeks of CBT and waiting time, respectively. Patients with MD demonstrated worse cognitive performance than healthy controls in verbal learning, recognition, and memory at baseline. After treatment, we found no improvements concerning verbal learning and memory performance compared with WL, with the exception of recognition memory. No differences were found between CBT conditions. Psychological treatments such as CBT seem to have limited influence on memory functions. Concerning recognition memory, our results contradict, in part, previous assumptions that cognitive impairments persists despite depressive symptom reduction.

Comparing the Efficacy of CBASP with Two Versions of CBT for Depression in a Routine Care Center: A Randomized Clinical Trial.

BACKGROUND: The cognitive-behavioral analysis system of psychotherapy (CBASP) was developed for the treatment of chronic, early-onset depression. However, it is unclear whether this approach can be recommended for depression in general (episodic and chronic), and no direct comparisons between CBASP with different versions of cognitive-behavioral therapy (CBT) exist. METHODS: A randomized controlled trial compared 3 treatment conditions (all lasting 16 sessions) with a waiting list group (WL): CBASP, CBT with a focus on physical exercise (CBT-E), and CBT with a focus on pleasurable, low-energy and mindful activities (CBT-M). We included 173 patients and involved 41 therapists. Assessments were at baseline, after session 8, and at the end of treatment. RESULTS: Our primary outcome Beck Depression Inventory-II indicated a general advantage of the CBT arms compared to CBASP [F(6, 154.5) = 4.2, p = 0.001], with significant contrasts in particular in favor of CBT-E. Effect sizes against WL were d = 0.91 (CBT-E), 0.87 (CBT-M), and 0.47 (CBASP). A triple interaction with an additional factor "chronic versus episodic depression" [F(6, 142.7) = 2.2, p = 0.048] indicated that the treatments resulted in different outcomes, with best results again for CBT-E in particular in episodic depression. Responder rates indicated significant improvements (56% in both CBT arms, 34% in the CBASP arm, 3.4% in WL; intention-to-treat samples). As compared to CBASP, response rates were significantly higher for CBT-E (OR = 2.48; 95% CI = 1.02-6.00) and CBT-M (OR = 2.46; 95% CI = 1.01-6.01). CONCLUSIONS: CBASP was more effective than WL, but less effective than the 2 CBT arms. This was mainly caused by an advantage of CBT interventions in episodic depression.

Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics.

Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

Childhood adversity and cognitive functioning in patients with major depression.

OBJECTIVE: Major depression is often accompanied by deficits in cognitive functioning and lowered executive functions. However, not all depressed patients show impairments in these domains. The aim of this study was to examine whether different kinds of childhood adversity might account for cognitive deficits in patients with major depression. METHODS: Ninety-one patients with major depression (DSM-IV) and 40 healthy controls completed a neuropsychological test battery assessing memory, processing speed and executive functions. The Childhood Trauma Questionnaire (CTQ) was used to measure the severity and number of incidences of sexual, physical and emotional abuse and physical and emotional neglect. RESULTS: Patients with major depression had a significantly higher number of traumas and reported more severe emotional abuse, emotional neglect and physical neglect than healthy controls. Patients performed less well in memory tasks, general knowledge and processing speed than healthy controls. Hierarchical regression analyses indicated that the overall number of traumas was significantly associated with poorer general knowledge, lower processing speed and impaired executive functions in patients with major depression. A second model including all CTQ-subscales simultaneously demonstrated an association between physical neglect and poorer verbal learning, and physical abuse and diminished executive functions. CONCLUSION: A higher number of childhood adversities may influence general knowledge, processing speed and executive functions in patients with major depression. In addition, physical abuse and neglect seemed to be associated with verbal learning deficits and poorer executive functions.

Blunted exercise-induced mobilization of monocytes in somatization syndromes and major depression.

BACKGROUND: Previous research indicates that physical activity may alter the number of immune cells. We examined whether increasing or decreasing the level of physical activity affects circulating lymphocyte and monocyte counts in patients with somatization syndromes and patients with major depression. METHODS: Thirty-eight participants with major depression, 26 participants with somatization syndromes and 47 healthy controls participated in the study. Using an experimental within-subject design, participants were involved in 1 week of increased physical activity (daily exercise sessions) and 1 week of reduced physical activity. Counts of total lymphocytes, lymphocyte subsets and monocytes were determined before and after each trial. Linear mixed models adjusted for sex, body mass index, age, fitness status and the order of trials were used for longitudinal data analysis. RESULTS: One week of exercise increases the number of monocytes in healthy controls (p<.05), but not in patients with somatization syndromes or patients with major depression. In addition, after 1 week of exercise, depressive symptoms were reduced in patients with major depression (p<.05) while somatoform symptoms were reduced (p<.05) in both clinical groups. Baseline comparisons and mixed models indicated reduced T helper cell counts in patients with somatization syndromes. LIMITATIONS: Relatively small sample size. The time of physical activity was relatively short and restricted to low-graded exercise. CONCLUSIONS: This study demonstrates a blunted mobilization of monocytes by exercise in both patients with somatization syndromes and patients with major depression. In addition, even one week of exercise reduces somatoform and depressive symptoms.

The predictive value of somatic and cognitive depressive symptoms for cytokine changes in patients with major depression.

CONTEXT: Elevated concentrations of proinflammatory cytokines have been hypothesized as an important factor in the pathophysiology of depression. Depression itself is considered to be a heterogeneous disorder. Current findings suggest that "cognitive" and "somatic" symptom dimensions are related to immune function in different ways. So far, little research has been done on the longitudinal aspects of inflammation in patients with major depression, especially with respect to different symptom dimensions of depression. Therefore, we investigated which aspects of depression may predict changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 over 4 weeks. METHODS: Forty-one patients with major depression diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 45 healthy controls were enrolled. Serum measurements of TNF-alpha and IL-6 were conducted at baseline and 4 weeks later. Psychometric measures included the assessment of cognitive-affective depressive symptoms and somatic symptoms during the last 7 days as well as somatic symptoms during the last 2 years. RESULTS: Patients with depression showed increased levels of TNF-alpha (P<0.05) compared to healthy controls. Hierarchical regression analyses indicated that neither depressive nor somatic symptoms predict changes in proinflammatory cytokines in the whole sample of depressed patients. Moderation analyses and subsequent sex-stratified regression analyses indicated that higher somatoform symptoms during the last 2 years significantly predict an increase in TNF-alpha in women with major depression (P<0.05) but not in men. Exploratory analyses indicated that the stability of TNF-alpha and IL-6 (as indicated by intraclass correlation coefficients) over 4 weeks was high for TNF-alpha but lower for IL-6. CONCLUSION: The present study demonstrated that a history of somatoform symptoms may be important for predicting future changes in TNF-alpha in women with major depression.

Increased soluble interleukin-2 receptor levels are related to somatic but not to cognitive-affective features in major depression.

Cell-mediated immune activation may play a role in the pathogenesis of depression as indicated by findings of increased soluble tumor necrosis factor receptor (sTNF-R) levels and meta-analytic evidence for elevated soluble interleukin-2 receptor (sIL-2R) concentrations. However, little research has been done on how these soluble cytokine receptors are differently related to specific features in patients with depression. We measured levels of the soluble cytokine receptors sIL-2R, sTNF-R1 and sTNF-R2 in 25 non-medicated patients with major depression (DSM-IV) and 22 healthy controls. Psychometric measures included cognitive-affective depressive symptoms, somatoform symptoms, somatic and cognitive dimensions of anxiety and current mood states. While patients with depression showed increased levels of sIL-2R (p<0.01), differences in sTNF-R1 (p=0.09) and sTNF-R2 (p=0.08) marginally failed to reach significance. Increased concentrations of sIL-2R were related to somatic measures such as the severity of somatoform symptoms and somatic anxiety symptoms but not to cognitive-affective measures or current mood states. Our findings may suggest some specificity in the relationship between sIL-2R and symptom dimensions and highlight potential pathways by which T cell mediated immune activation may underpin somatic symptoms in depression.