Can variation in hypothalamic-pituitary-adrenal (HPA)-axis activity explain the relationship between depression and cognition in bipolar patients?

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. METHODOLOGY/PRINCIPAL FINDINGS: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. CONCLUSIONS/SIGNIFICANCE: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

Insight in bipolar disorder: associations with cognitive and emotional processing and illness characteristics.

OBJECTIVE: To investigate the multifactorial relationship between illness insight, cognitive and emotional processes, and illness characteristics in bipolar disorder patients. METHODS: Data from 85 euthymic or mildly to moderately depressed bipolar disorder patients were evaluated. Insight was measured using the Mood Disorder Insight Scale (total score and subscale scores: awareness of illness, symptom attribution, and need for treatment). Cognitive and emotional functioning was measured in four domains (processing speed, memory, executive functioning, and emotional learning) in addition to premorbid IQ. Illness characteristics were assessed using the Mini-International Neuropsychiatric Interview, the Questionnaire for Bipolar Disorder, and the Inventory of Depressive Symptomatology-self rating scale. Regression analyses were performed for the whole sample. Post-hoc, interactions with lifetime psychotic features (LPF) were statistically tested and if significant, analyses were repeated for patients with (n = 36) and without (n = 49) LPF separately. RESULTS: In the whole group, better insight was associated with lower processing speed, better memory performance, increased emotional learning, higher level of depressive symptoms, and longer duration of illness. Patients with LPF had worse awareness of illness, but better symptom attribution than patients without LPF. No group differences for need for treatment and overall insight were found. Finally, processing speed significantly predicted subscores for symptom attribution in patients with LPF only. CONCLUSIONS: Cognitive functioning as well as impairments in emotional learning and psychotic features independently contributes to impaired insight in bipolar disorder. Processing speed seems to be a key variable in the prediction of insight in patients with LPF and not in patients without LPF.

Is the lack of association between cognitive complaints and objective cognitive functioning in patients with bipolar disorder moderated by depressive symptoms?

OBJECTIVES: To investigate the association between cognitive complaints and objective cognitive functioning in bipolar patients, with a focus on the moderating role of depressive symptoms. METHODS: The association between cognitive complaints (measured by the total score and four subscales of the Cognitive Failure Questionnaire; CFQ) and objective cognitive functioning (domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory and executive functioning/working memory, and the total score) was assessed in 108 euthymic (n=45) or mildly to moderately depressed bipolar patients (n=63). We studied potential moderation of this association by depressive symptoms (total score of the Inventory of Depressive Symptomatology-self rating). Analyses were performed using Pearson correlations and multiple linear regression. RESULTS: Cognitive complaints were not associated with objective cognitive functioning, except for CFQ 'memory for names' which was positively correlated with speed of information processing (r=0.257, p=0.007). Although depressive symptoms were positively associated with cognitive complaints (total score and three subscales; p<0.01), the association between cognitive complaints and objective cognitive functioning was not moderated by depressive symptoms (p for interaction 0.054 to 0.988). LIMITATIONS: It can be argued whether the retrospective questionnaire (CFQ) is sufficiently accurate to measure the type of cognitive dysfunctions seen in bipolar patients. CONCLUSIONS: Cognitive complaints are not associated with objective cognitive functioning, irrespective of depressive symptoms. However, cognitive complaints are indicative for depressive symptoms. Clinicians should be to be alert to depressive symptoms rather than objective cognitive problems in patients expressing cognitive complaints.

Cognitive functioning in patients with bipolar disorder: association with depressive symptoms and alcohol use.

BACKGROUND: Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored. METHODOLOGY/PRINCIPAL FINDINGS: The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R(2) 7%), speed of information processing (adjusted beta 0.36; R(2) 20%), attentional switching (adjusted beta 0.24; R(2) 16%) and the mean score (adjusted beta 0.23; R(2) 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction. CONCLUSIONS/SIGNIFICANCE: Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia.

The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

Long-term memory deficits in schizophrenia: primary or secondary dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance.

Schizophrenic patients without neuropsychological deficits: subgroup, disease severity or cognitive compensation?

Some schizophrenic patients do not show clinically relevant cognitive deficits. The question remains whether this represents the existence of an etiologically different subgroup, a general effect of disease severity or whether their cognitive deficits do not reach a clinical threshold due to a greater cognitive compensation ('brain reserve') capacity. A group of 23 out of 118 first onset patients was identified as cognitively normal (CN). The cognitive profile of these patients was compared with that of 45 healthy controls. Next these patients were compared with the cognitively impaired (CI) patients on obstetric complications (OCs), premorbid adjustment, age at onset, Positive and Negative Syndrome Scale ratings, social functioning and substance abuse. In addition both groups were compared on intelligence and educational level as indirect indicators of cognitive compensation capacity. There were no differences in OCs, premorbid adjustment, age at onset, psychopathology or substance abuse between the two patient groups. There was a significant difference in social functioning, which is a consequence rather than a cause of cognitive deficits. However, the CN patients scored significantly higher on measures of intelligence and educational level than the CI patients. This suggests that a difference in cognitive compensation capacity could explain the existence of a CN patient group.