Cognitive functioning, cortisol release, and symptom severity in patients with schizophrenia

Department of Psychology (DJW, EFW), Emory University, Atlanta, Georgia 30322, USA.
Biological Psychiatry (Impact Factor: 10.25). 01/2001; 48(12):1121-32. DOI: 10.1016/S0006-3223(00)01052-0
Source: PubMed

ABSTRACT There is substantial evidence of dysregulation of cortisol secretion, hippocampal abnormalities, and memory deficits in schizophrenia and other psychotic disorders. Research also suggests that cortisol secretion augments dopaminergic activity, which may result in increased symptom expression in this clinical population.
We examined the relations among cortisol release, cognitive performance, and psychotic symptomatology. Subjects were 18 adults with schizophrenia or schizoaffective disorder, seven with a nonpsychotic psychiatric disorder, and 15 normal control subjects. Tests of memory and executive function were administered. Cortisol was assayed from multiple saliva samples.
Findings indicated the following: 1) patients with psychotic disorders scored below the comparison groups on the cognitive measures; 2) for the entire sample, cortisol levels were inversely correlated with performance on memory and frontal tasks; and 3) among patients, cortisol levels were positively correlated with ratings of positive, disorganized, and overall symptom severity, but not with negative symptoms.
The present results suggest that abnormalities in the hypothalamic-pituitary-adrenal axis and hippocampal systems play a role in observed cognitive deficits across populations. Among psychotic patients, elevated cortisol secretion is linked with greater symptom severity.

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Available from: Rich Lewine, Jul 30, 2015
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    • "For example, basal cortisol levels are higher in patients with manic psychoses than in patients with schizophrenia (Christie et al., 1986); the post-mortem distribution of glucocorticoids receptors in the central nervous system is decreased in both patients with schizophrenia and those with bipolar disorder, but it differs according to anatomical site in the two diagnostic groups (Webster et al., 2002); and HPA axis responses to pharmacological challenges is different among different subtypes of schizophrenia (Duval et al., 2003). When examining populations with mixed diagnoses (schizophrenia and affective psychoses), two studies did not find significant associations between cortisol levels and specific symptoms (Pruessner et al., 2008; Garner et al., 2011) and one found an association with both positive symptoms and disorganization (Walder et al., 2000). Christie and colleagues compared subgroups of patients with different diagnoses of psychotic disorders, at various stages of the illness: in their study, cortisol levels correlated positively with the severity of positive symptoms irrespective of the diagnosis, but they also correlated with negative symptoms in schizophrenia, with depressive symptoms in depressive psychoses, and with excitement symptoms in manic psychoses (Christie et al., 1986). "
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    ABSTRACT: Abnormalities in hypothalamic-pituitary-adrenal (HPA) axis activity have been reported in patients with psychosis, but it is still unclear how these are related to the clinical symptomatology. Inconsistent findings have emerged from previous studies on the association between cortisol levels and clinical symptoms. Methodological and/or clinical factors, such as patients' diagnosis or illness phase, might partially account for these inconsistencies. The aim of this study was to investigate the association between HPA axis activity and clinical symptoms in first-episode psychosis, taking into account diagnosis and illness phase. Saliva samples were collected in 55 subjects with first-episode psychosis to assess the Cortisol Awakening Response (CAR) and diurnal cortisol levels (AUC-DAY). Severity of symptoms was assessed with the Positive and Negative Syndrome Scale (PANSS). Scores for subscales and symptom dimensions were used as predictors in multivariate analyses in different diagnostic subgroups and in clinically remitted patients. In addition, a systematic review of the literature on this topic was conducted. In subjects with schizophrenia (n=36), the CAR was predicted by the severity of positive symptoms (beta=0.47, p=0.04); in subjects with depressive psychoses (n=8) the CAR was predicted by excitement (beta=0.58, p=0.005), disorganization (beta=0.39, p=0.007) and depressive symptoms (beta=0.32, p=0.005). In patients with bipolar psychoses (n=11) AUC-DAY was predicted negatively by disorganization (beta=-2.82, p=0.009) and positively by excitement (beta=2.06, p=0.009) and positive symptoms (beta=1.28, p=0.02). In the sample in clinical remission (n=9), the CAR was associated with the severity of positive symptoms (beta=1.34, p=0.009) and, negatively, with excitement (beta=-1.05, p=0.04). The systematic review (on a total of 28 papers, including n=1022 patients), found that in patients with psychosis cortisol levels have been associated with the severity of multiple symptom dimensions. HPA axis activity is associated with the severity of multiple types of symptoms in first-episode psychosis. Patients' diagnosis and clinical phase partially influence these associations.
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    • "Moreover, patients with psychotic depression, who have increased cortisol levels in the evening and night, show impaired verbal memory when compared not only with normal controls but also with nonpsychotic depressed patients (Belanoff et al. 2001), and show correlations between higher cortisol levels and poorer verbal memory and processing speed (Gomez et al. 2006). Similar findings have been described in patients with schizophrenia (Walder et al. 2000; Halari et al. 2004) or bipolar disorder (Young et al. 2004). Although it is somewhat surprising that we did not find a relationship between cortisol levels during the day and (worse) cognitive function in FEP, we should emphasize that the cortisol values in our samples were only mildly elevated. "
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    ABSTRACT: Cognitive impairment, particularly in memory and executive function, is a core feature of psychosis. Moreover, psychosis is characterized by a more prominent history of stress exposure, and by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In turn, stress exposure and abnormal levels of the main HPA axis hormone cortisol are associated with cognitive impairments in a variety of clinical and experimental samples; however, this association has never been examined in first-episode psychosis (FEP). In this study, 30 FEP patients and 26 controls completed assessment of the HPA axis (cortisol awakening response and cortisol levels during the day), perceived stress, recent life events, history of childhood trauma, and cognitive function. The neuropsychological battery comprised general cognitive function, verbal and non-verbal memory, executive function, perception, visuospatial abilities, processing speed, and general knowledge. Patients performed significantly worse on all cognitive domains compared to controls. In patients only, a more blunted cortisol awakening response (that is, more abnormal) was associated with a more severe deficit in verbal memory and processing speed. In controls only, higher levels of perceived stress and more recent life events were associated with a worse performance in executive function and perception and visuospatial abilities. These data support a role for the HPA axis, as measured by cortisol awakening response, in modulating cognitive function in patients with psychosis; however, this association does not seem to be related to the increased exposure to psychosocial stressors described in these patients.
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    • "Executive functions are those that require higher levels of cognitive processing (e.g., abstraction, planning, strategic control of cognitive resources such as those found in task inhibition, set shifting, suppressing interference). Consistent with this suggestion, some associations between cortisol, executive and other non-episodic memory functions have been found (Lee et al., 2007; Li et al., 2006; Lupien et al., 1994; Lupien et al., 1999a; Newcomer et al., 1999; Walder et al., 2000; Young et al., 1999). "
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