Walder DJ, Walker EF, Lewine RJ. Cognitive functioning, cortisol release, and symptom severity in patients with schizophrenia. Biol Psychiatry 48: 1121-1132

Department of Psychology (DJW, EFW), Emory University, Atlanta, Georgia 30322, USA.
Biological Psychiatry (Impact Factor: 10.26). 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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    • "Among different biological factors, hormones may play an important role in the pathogenesis of cognitive impairment in psychotic disorders. Most studies have focused on cortisol (Walder et al., 2000), although others, such as thyroid hormones, are also important . Thyroid hormones play an important role in the differentiation and growth of a healthy human brain and consequently in cognition. "
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    ABSTRACT: Subjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic-pituitary-thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis. We studied 70 patients with a psychotic disorder (<3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder). In patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis. Our study suggests that FT4 levels are associated with cognitive abilities (attention/vigilance and overall cognition) in individuals with early psychosis. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 05/2015; 166(1-3). DOI:10.1016/j.schres.2015.04.030 · 3.92 Impact Factor
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    • "This study found a strong negative correlation between dexamethasone abnormalities (dexamethasone non-suppressors) and cognitive performance in type II schizophrenics, implying a relationship between HPA axis hyperactivity and cognitive impairment. Furthermore, Walder et al. (61), evaluating 18 patients with chronic psychosis, 7 patients without psychosis, and 19 healthy controls, found that, in the entire sample, cortisol levels were negatively correlated with performance on memory and executive tasks. "
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    ABSTRACT: Objective: To carry out a systematic review of the literature addressing cognitive functions in first-episode psychosis (FEP), divided into domains. Although this is not a full “cognitive-genetics-in-schizophrenia review,” we will also include putative ideas of mechanism(s) behind these impairments, focusing on how early stress, and genetic vulnerability may moderate cognitive function in psychosis. Method: Relevant studies were identified via computer literature searches for research published up to and including January 2013, only case-control studies were included for the neurocognitive meta-analysis. Results: Patients with FEP present global cognitive impairment compared to healthy controls. The largest effect size was observed for verbal memory (Cohen’s d effect size = 2.10), followed by executive function (effect size = 1.86), and general IQ (effect size = 1.71). However, effect sizes varied between studies. Conclusion: Cognitive impairment across domains, up to severe level based on Cohen’s effect size, is present already in FEP studies. However, differences in levels of impairment are observed between studies, as well as within domains, indicating that further consolidation of cognitive impairment over the course of illness may be present. Cognitive abnormalities may be linked to a neurodevelopmental model including increased sensitivity to the negative effect of stress, as well as genetic vulnerability. More research on this field is needed.
    Frontiers in Psychiatry 01/2014; 4:182. DOI:10.3389/fpsyt.2013.00182
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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.
    Psychoneuroendocrinology 09/2011; 37(5):629-44. DOI:10.1016/j.psyneuen.2011.08.013 · 4.94 Impact Factor
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