Associations between cognitive performance and cortisol reaction to the DEX/CRH test in patients recovered from depression.

BACKGROUND: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in major depression (MDD) is one of the most reliably reported neurobiological characteristics of affective disorders. Whether these alterations in HPA axis regulation are limited to the acute stage of MDD or whether they persist after recovery, remains ambiguous. A relationship between hypercortisolemia and cognitive dysfunction in acutely depressed patients has been repeatedly observed and it was also demonstrated in a number of studies that a discrete cognitive impairment often persists in the remitted state of depression. In the present study we were interested, whether these subtle impairments in cognitive functioning observed in patients recovered from depression compared to healthy control subjects are associated with HPA axis feedback sensitivity. METHODS: In 20 recovered patients and 20 matched healthy controls we assessed HPA axis feedback sensitivity with the combined dexamethasone suppression/corticotropin-releasing-hormone (DEX/CRH) challenge test. Furthermore cognitive performance was investigated with respect to the following domains: verbal memory (Auditory Verbal Learning Test, VLMT), attention and executive control (Trail Making Test, TMT-A/B) as well as verbal fluency (Controlled Oral Word Association Test, COWAT). RESULTS: Recovered patients showed a significantly poorer cognitive performance compared to healthy controls (all p<.05). With regard to HPA-axis activity, no overall difference was observed in the DEX/CRH test between recovered patients and controls. In recovered patients however, a significant association was observed between cortisol response and verbal memory (main effect VLMT trial 1-5: p=.046), attention (main effect TMT-A: p=.015) and executive functioning in terms of set shifting (interaction samples*TMT-B: p=.018). Poorer test performance was related to increased cortisol levels in response to challenge. CONCLUSIONS: The present findings suggest that patients recovered from MDD are especially vulnerable toward detrimental effects of subtle HPA axis disturbances on cognitive performance.

Persistent non-verbal memory impairment in remitted major depression - caused by encoding deficits?

BACKGROUND: While neuropsychological impairments are well described in acute phases of major depressive disorders (MDD), little is known about the neuropsychological profile in remission. There is evidence for episodic memory impairments in both acute depressed and remitted patients with MDD. Learning and memory depend on individuals' ability to organize information during learning. This study investigates non-verbal memory functions in remitted MDD and whether nonverbal memory performance is mediated by organizational strategies whilst learning. METHODS: 30 well-characterized fully remitted individuals with unipolar MDD and 30 healthy controls matching in age, sex and education were investigated. Non-verbal learning and memory were measured by the Rey-Osterrieth-Complex-Figure-Test (RCFT). The RCFT provides measures of planning, organizational skills, perceptual and non-verbal memory functions. For assessing the mediating effects of organizational strategies, we used the Savage Organizational Score. RESULTS: Compared to healthy controls, participants with remitted MDD showed more deficits in their non-verbal memory function. Moreover, participants with remitted MDD demonstrated difficulties in organizing non-verbal information appropriately during learning. In contrast, no impairments regarding visual-spatial functions in remitted MDD were observed. LIMITATIONS: Except for one patient, all the others were taking psychopharmacological medication. The neuropsychological function was solely investigated in the remitted phase of MDD. CONCLUSIONS: Individuals with MDD in remission showed persistent non-verbal memory impairments, modulated by a deficient use of organizational strategies during encoding. Therefore, our results strongly argue for additional therapeutic interventions in order to improve these remaining deficits in cognitive function.

Implicit and explicit procedural learning in patients recently remitted from severe major depression.

In acute depression a high prevalence of deficits in learning and memory performance has been reported. Still, it is unclear whether these cognitive deficits are present after remission of clinical symptoms of depression. The present study compared 20 inpatients recently remitted from severe major depressive disorder (MDD) with 20 healthy matched control participants on two sequence learning tasks: a modified serial reaction-time task (SRT) for implicit learning, which is sensitive to subcortical and frontal impairments, and a serial generation task (SGT) for explicit learning. As compared with performance in healthy controls, implicit and explicit learning were not impaired in recently remitted inpatients with depression. Intentional acquisition of new information was related to the severity of depressive symptoms as patients with higher scores on Beck's Depression Inventory (BDI) showed poorer explicit learning. In contrast to findings in acute depression, our results suggest a normal degree of learning in remitted depression; these findings are consistent with unimpaired fronto-striatal functioning. However, although not statistically significant, patients remitted from melancholic MDD revealed poorer implicit learning performance compared with patients remitted from non--melancholic MDD. Longitudinal studies in patients with melancholic vs. non-melancholic MDD are needed to investigate the course of cognitive functioning during the recovery from MDD.

Occurence of ultra-rapid cycling during electroconvulsive therapy in bipolar depression.

BACKGROUND: Treatment of bipolar depression with antidepressants has often been reported to be associated with a certain risk of rapid cycling (RC). Also, non-pharmacological treatment approaches such as sleep deprivation or light therapy can induce affective shifts. Moreover, during electroconvulsive therapy (ECT), which is considered a powerful antidepressant treatment, manic switches and episodes of rapid cycling can occur. METHODS: Here we report the case of a 66-year-old female patient with bipolar depression, who underwent electroconvulsive therapy because of a therapy-refractory depressive episode. RESULTS: During ECT, highly frequent mood alternations were observed, fulfilling the criteria of ultra rapid cycling (URC). These symptoms were successfully treated with lithium carbonate while ECT was continued. CONCLUSION: To our knowledge, this is the first case report of URC during ECT. URC might be considered a rare but potential side effect of ECT. In our case, lithium was used successfully for the treatment of URC and might be suggested in similar cases, where anticonvulsants are not the first choice of treatment. However, in view of the risk of cognitive side effects the combination of ECT and lithium requires a careful clinical monitoring.

Working-memory fMRI reveals cingulate hyperactivation in euthymic major depression.

While cognitive impairments are well documented for the acute episode of major depressive disorder (MDD), less is known about cognitive functioning in the euthymic state. For working memory, dysfunctional activation of lateral prefrontal and cingulate cortex has been reported in the acute episode. This study investigates working-memory function and its neurobiological correlate in euthymic MDD patients, particularly whether dysfunctional activation persists when depressive symptoms improve. We investigated 56 subjects with functional magnetic resonance imaging (fMRI) at 3 Tesla. To challenge working-memory function, a classical verbal n-back task (0-, 1-, and 2-back) was used in 28 well-characterized, euthymic, unipolar MDD patients and 28 healthy control subjects matched according to age, sex, and educational level. Data were analyzed using SPM5. In the absence of significant behavioral differences, we observed comparable overall patterns of brain activation in both groups. As expected, both groups showed stronger activation of the typical working-memory network with increasing memory load. However, significant hyperactivation of the cingulate cortex was observed in euthymic patients, while lateral prefrontal activation was comparable between patients and controls. Working-memory challenge in the euthymic state of MDD revealed a dissociation of lateral prefrontal and cingulate brain function. Cingulate function, which is important for both emotional and cognitive processing and their integration, is still abnormal when mood is restored. This could reflect a different speed of normalization in prefrontal and limbic cortices, persistent systematic changes in neuronal networks after an episode of MDD, or a compensatory mechanism to maintain working-memory performance.

Therapeutic strategies for catatonia in paraneoplastic encephalitis.

This report is about a 40-year-old man suffering from fluctuating catatonia as main symptom of long-lasting paraneoplastic encephalitis caused by a testicular neoplasm. With recurrence of a neoplasm initially diagnosed as seminoma after a 7-year symptom-free interval the patient suddenly developed various neurological and psychopathological symptoms including seizures, autonomic dysregulation, continuous anterograde short-term amnesia and predominantly a long-lasting complex catatonic syndrome with on-off phenomena. Repeated MRI scans of the brain showed no pathology; brain FDG-PET scans indicated a hypometabolism of the frontal cortex and the left temporal lobe. Eventually a paraneoplastic encephalitis was diagnosed. Repeated resections of tumour recurrences and plasmapheresis moderately alleviated catatonic symptoms. Haloperidol and lorazepam effectively relieved catatonic symptoms in contrast to various atypical antipsychotic drugs and diazepam. A series of 12 electroconvulsive treatments (ECT) temporarily improved residual catatonic symptoms such as catalepsy, stupor and mutism. Further neoplasm recurrences, however, reinforced catatonia until the tumour was successfully treated and the patient fully recovered. This case report illustrates the potential but also the limitations of various therapeutic approaches in organic catatonia due to paraneoplastic encephalitis.