*Title Page
Title: Associations between diurnal cortisol patterns and lifestyle factors, psychotic symptoms, and neurological deficits: A longitudinal study on patients with chronic schizophrenia
Authors: Rainbow T. H. Hoab*, Ted C. T. Fonga, Adrian H. Y. Wana, Friendly S. W. Au-Yeungc, Eric Y. H. Chend, David Spiegele
Affiliations: a Centre on Behavioral Health, The University of Hong Kong, Hong Kong. b
Dept of Social Work & Social Administration, The University of Hong Kong, Hong Kong.
c
The Providence Garden for Rehab, Hong Kong Sheng Kung Hui Welfare Council Limited.
d
Dept of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong.
e
Dept of Psychiatry & Behavioral Sciences, Stanford University School of Medicine,
Stanford, CA
Correspondence: Rainbow Tin-hung Ho, Centre on Behavioral Health, 2/F, The Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong Phone no: 852-2831 5169; Email:
[email protected]; Fax no: 852-2816 6710
Running title: Diurnal cortisol patterns and lifestyle factors, psychotic symptoms, and neurological deficits
Keywords: Cortisol; Chronic schizophrenia; Diurnal slope; Stress; Psychotic symptoms; Chinese
Word count (exc. figures/tables): 3,544; number of tables: 3; number of figures: 2
Highlights (for review)
Highlights
Greater stress and BMI and less exercise predict reduced cortisol declines
Reduced cortisol declines predict greater positive and negative psychotic symptoms
Reduced cortisol declines are linked to greater motor and sequencing deficits
The results elucidate diurnal cortisol patterns in chronic schizophrenic patients
The HPA axis may mediate the effects of lifestyle factors on symptoms and deficits
*Manuscript clean version Click here to view linked References
Associations between diurnal cortisol patterns and lifestyle factors, psychotic symptoms, and neurological deficits: A longitudinal study on patients with chronic schizophrenia
Abstract The present study examined the relationships between diurnal cortisol patterns and perceived stress, lifestyle factors, psychotic symptoms, neurological deficits, and daily functioning in patients with chronic schizophrenia. The participants were 149 Chinese patients with chronic schizophrenia. Salivary cortisol was collected upon waking, before lunchtime, and before bedtime at baseline (Time 1). Self-reported measures on perceived stress and lifestyle factors such as body-mass index and daily exercise span were recorded at Time 1. Diagnostic assessments on psychotic symptoms, neurological deficits, and daily functioning were made at Time 1 and Time 2 (3 months later). Latent growth modeling and path modeling analysis were performed to investigate the diurnal cortisol patterns and the relationships with the study variables. Higher levels of perceived stress and body-mass index and less physical activity were significantly linked to reduced cortisol decline. Reduced cortisol decline at Time 1 significantly predicted greater psychotic (positive and negative) symptoms and more severe neurological deficits in motor coordination and sequencing of complex motor acts at Time 2. The present results contribute to a better understanding of the diurnal cortisol patterns among patients with chronic schizophrenia and the associations with lifestyle factors, 1
psychotic symptoms, and neurological deficits. The findings lend support to the neural diathesis–stress model and suggest that hypothalamic–pituitary–adrenal axis may potentially mediate the effects of lifestyle factors on psychotic symptoms and neurological deficits.
Keywords: Cortisol; Chronic schizophrenia; Diurnal slope; Stress; Psychotic symptoms; Chinese
1.
Introduction The hypothalamic–pituitary–adrenal (HPA) axis is a neuroendocrine system that plays a
central role in coordinating the stress response via the secretion of cortisol, a major steroid, to maintain homeostasis in various physiological systems (Gunnar and Quevedo, 2007). In normal individuals, cortisol levels display a typical circadian rhythm with an early morning peak upon waking, followed by a gradual decline throughout the day, and a rise during sleep (Turner-Cobb, 2005). Cortisol levels upon waking reflect basal cortisol without exposure to stressors and the diurnal cortisol slope reflects the fluctuation of cortisol levels throughout the day (Smyth et al., 1997). Evaluation of the circadian cortisol fluctuation is indicative of the HPA axis reactivity. Schizophrenia is a neuropsychiatric disorder that is attributable to multiple biological
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and environmental factors. The neural diathesis–stress model (Walker and Diforio, 1997) is widely adopted to explain how environmental stressors interact with preexisting biological vulnerability in the etiology of the disorder. This model proposes that psychosocial stress acts via the HPA axis to trigger or worsen the schizophrenic symptoms (Walker et al., 2004). Persistent stress exposure can lead to chronic elevations in cortisol release and impair the negative feedback system that dampens HPA activity (Walker et al., 2008). These could lead to overactivation in dopamine pathways and hyperactivity in dopamine neurotransmission (Dallman et al., 2004; Moghaddam, 2002), which could result in exacerbation of the psychotic symptoms. Compared with healthy controls, patients with schizophrenia manifest evident damage in the hippocampus, a brain region that regulates HPA activity via glucocorticoid receptors (Harrison, 2004). Heightened baseline cortisol and flattened diurnal curves in terms of reduced cortisol decline have been associated with greater symptom severity, poorer cognitive performance, and memory deficits in the patients (Goyal et al., 2004; Hempel et al., 2010; Ko et al., 2007; Lupien et al., 2005; Walder et al., 2000; Yilmaz et al., 2007). Despite the relationships between heightened cortisol and various prognostic indicators in schizophrenia, few studies have examined the prognostic value of the diurnal cortisol slope in mediating symptoms caused by stress exposure. Patients with chronic schizophrenia have shown HPA axis dysfunctions (Kaneko et al., 3
1992), heightened negative symptoms, and ill-health such as metabolic syndrome, diabetes mellitus and premature mortality (Bradley and Dinan, 2010; Gury, 2004; Laursen, 2011; Ryan and Thakore, 2002). Compared with patients with first-episode psychosis, chronic schizophrenia patients in general receive long-term treatment of antipsychotic medications. Antipsychotic treatment has shown dampening effects on HPA activation and normalizes diurnal cortisol hyper-secretion in schizophrenia patients (Mondelli et al., 2010; Walker et al., 2008). In particular, atypical antipsychotic medications have been found to produce significant improvements in clinical outcomes and HPA axis functioning over typical antipsychotic treatment in previous studies (Altamura et al., 1999; Cohrs et al., 2006; Zhang et al., 2005). Current research literature on schizophrenia focuses on its developmental course among first-episode or high-risk samples (Carol and Mittal, 2015; Cullen et al., 2014; Simeonova et al., 2015). Though these studies have contributed to a better understanding of its etiology and predictors of illness onset, given the high relapse rate and chronicity, it is essential to identify potential risk and protective factors of its long-term prognosis (Breier et al., 1991). Factors associated with a healthy lifestyle, namely, maintaining a normal body mass index (BMI) and being physically active, have been identified as predictors of better prognosis during antipsychotic treatments (Brown et al., 1999; Manzanares et al., 2014). Yet, research on the associations between the lifestyle factors and diurnal cortisol patterns in patients with chronic 4
schizophrenia has been scarce. The present longitudinal study aimed to investigate the associations between diurnal cortisol patterns and lifestyle factors, symptom severity, neurological deficits, and daily functioning in patients with chronic schizophrenia. The first hypothesis was that higher levels of perceived stress contribute to HPA axis dysfunctions. The second hypothesis was that HPA axis dysfunctions predict greater psychotic symptoms and neurological deficits, and poorer daily functioning. The third hypothesis was that lifestyle factors (BMI and physical activity) are significantly associated with diurnal cortisol patterns. The present study took into account the influences of chronicity and antipsychotic treatment as likely confounding factors of the HPA axis activity. Figure 1 shows the conceptual model of the present study. [Figure 1 about here]
2.
Methods
2.1. Participants The present study adopted a longitudinal study design and recruited 149 patients with chronic schizophrenia who were institutionalized in a mental health rehabilitation complex in Hong Kong in January 2014 (Time 1). The data analyzed in this study originated from a randomized controlled trial of Taichi and exercise interventions on chronic schizophrenia patients. The rehabilitation complex provides long-term care and halfway house services to 5
the patients. The inclusion criteria of the participants were fulfillment of the DSM IV-TR criteria for schizophrenia as diagnosed by a psychiatrist, aged 18-65 years, and ability to understand and speak Cantonese. The exclusion criteria included relapses in schizophrenia that required hospitalization, suffering from severe schizophrenic symptoms (such as persistent withdrawal) that would limit their ability to interact in the assessment interview, a history of organic mental disorder, i.e. decreased mental function due to a medical disease (such as delirium, dememtia, or brain trauma) other than a psychiatric illness, presence of physical disabilities or other severe illnesses that may impair cognitive or visuo-motor functioning. The participants completed follow-up assessments on psychotic and neurological symptomatology as well as daily functioning three months later (Time 2).
2.2. Procedures The study was carried out in accordance with the latest version of the Declaration of Helsinki and the study design was reviewed by the local institutional review board. Written informed consent was obtained from the participants after the nature, risks, and benefits of the study procedures had been fully explained during the screening interview. The participants completed a saliva collection protocol, a self-report questionnaire on daily functioning and diagnostic assessments on psychiatric symptoms and neurocognitive deficits. Their heights and weights were measured to compute the body mass index (BMI, kg/m2) with 6
the following cut-off limits for Asians: underweight (< 18.5), normal (18.5–22.9), overweight (23.0–27.5), and obese (> 27.5) (WHO, 2004). In addition to demographic characteristics (age, gender, education level, and marital status) and daily exercise spans, data on medication was collected from the patients’ personal record which provided information on the type of antipsychotic medications received by the participants, duration of psychiatric diagnosis, and their medication dosage.
2.3. Salivary cortisol assessment Written instructions and verbal explanations were provided to the participants on collection of saliva samples using cotton salivette tubes in the hostel at three occasions at Time 1: upon waking, before lunch and before bedtime. Since the participants were residing in the institution, they followed a stable daily routine and fixed meal schedule. They were reminded to collect the first saliva sample immediately upon awakening, to avoid food consumption for 30 min prior to sample collection, and to avoid strenuous exercise to avoid distorting the results. To improve adherence to the collection protocol, we provided instruction sheets and briefing sessions for the ward attendants on the day of data collection. The participants were instructed to record their time of collection of each sample on a time sheet that provided the sampling instructions. The collected salivette tubes were kept frozen at the laboratory. Cortisol levels were determined after thawing and centrifugation at 3000 7
rpm for 15 min using the ELISA kit (Salimetrics, PA, USA). The intra-assay and inter-assay variation was less than 10%. Of the 447 collected saliva samples, 414 (92.6%) provided valid cortisol values. Data analyses were based on 399 of the 414 valid samples (96.4%) after screening for outliers (>3 SD deviations from the mean). The diurnal cortisol slope was used in this study as the main summary variable for the cortisol measures. To provide a more thorough description of the diurnal cortisol pattern, we also calculated the mean cortisol level as the average of the three cortisol measures and the area-under-the-curve (AUC) with respect to ground as an indicator of the total diurnal concentration
2.4. Measures Psychosocial stress was assessed by the Chinese Perceived Stress Scale (Cohen et al., 1983; Ng, 2013) at Time 1. This 10-item, 5-point self-report instrument measures how often participants experience feelings of stress within the past month. The total score (α = .71) ranges from 0 to 40, with a higher score denoting higher stress. Psychiatric symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987) based on semi-structured interviews at Time 1 and Time 2. The 7-point Chinese PANSS (Fong et al., 2015) assesses positive (4 items, α = .84) and negative (5 items, α = .83) symptoms exhibited in the past week. The total score ranges from 4 to 28 for positive symptoms and 5 to 35 for negative symptoms with higher scores indicating more pronounced symptoms. 8
The Chinese version of the Neurological Evaluation Scale (Buchanan and Heinrichs, 1989) was used to assess motor deficit (α = .80) and sequencing deficit (α = .59) at Time 1 and Time 2. The task performance of the participants was rated on a 3-point scale based on the number of mistakes. The total scores for motor and sequencing deficits range from 0 to 12 and 0 to 6, respectively, with higher scores indicating greater deficits. Daily functioning was measured by the Chinese version of Barthel’s Activities of Daily Living (ADL) index (Mahoney and Barthel, 1965) at Time 1 and Time 2. This self-report scale evaluates basic self-care via a list of 10 tasks such as feeding, bathing, and bladder continence. The total score for the ADL (α = .71) ranges from 0 to 100, with a higher score denoting better functioning in daily life.
2.5. Data analysis Latent growth modeling with a latent time basis (McArdle and Bell, 2000) was used to determine the waking cortisol and diurnal cortisol slope for the cortisol data. The robust maximum likelihood estimator was used to account for the non-normal cortisol data (Muthén and Muthén, 1998-2013). A normal diurnal cortisol profile is characterized by a steeper (more negative) diurnal slope with substantial decreases in cortisol levels throughout the day. In contrast, flattened (less negative) diurnal slopes indicate reduced diurnal decreases in cortisol and reflect potential dysfunctions in HPA axis. Missing data were handled via full 9
information maximum likelihood estimation under missing-at-random assumption (Schafer and Graham, 2002). Model fit was evaluated based on the following criteria: insignificant χ2 (p > 0.05), comparative fit index (CFI) ≥ 0.95, and root mean square error of approximation (RMSEA) and standardized root mean square residual (SRMR) ≤ 0.05. We performed path analyses to investigate the relationships between the diurnal cortisol pattern and the study variables. First, we examined the concurrent associations between the diurnal cortisol pattern and perceived stress, BMI, and daily exercise at Time 1. Next, the diurnal cortisol pattern was used to predict the outcome variables (psychotic symptoms, neurological deficits, and daily functioning) at Time 2 controlling for the baseline status at Time 1. Confounding factors (gender, duration of psychiatric diagnosis, type of antipsychotic medications, and medication dosage) were included in the model as covariates. The proportion of explained variance (R-squared) was reported for each dependent variable, with “small,” “moderate,” and “large” effect sizes denoted by values of 0.02, 0.13, and 0.26, respectively (Cohen, 1988). Statistical significance was set at the 0.05 level.
3.
Results
3.1. Descriptive profiles of participants The participants were middle-aged and had an average time since psychiatric diagnosis of around 30 years. The majority of the sample were male, single, had secondary education 10
level, and received atypical antipsychotic medications such as clopazine, risperidone, olanzapine, or amisulpride. The mean BMI of the sample was 24.0 (SD = 4.1) with 9.4% of them found to be underweight, 39.2% overweight, and 18.8% obese. Table 1 displays the descriptive statistics of perceived stress, psychiatric symptoms, neurological deficits, and daily functioning. There were no significant changes in positive and negative symptoms (Cohen d = 0.03 – 0.13, p > .05) from Time 1 to Time 2. However, the sample showed significant decreases in motor and sequencing deficits and significant increases in daily functioning (Cohen d = 0.23 – 0.39, p < .01) across the 3-month period. [Table 1 about here]
3.2. Diurnal cortisol pattern at Time 1 Table 1 shows the descriptive statistics of the three cortisol samples. The corresponding collection time of the three saliva samples were on average 0601 h (SD = 39 min), 1145 h (SD = 31 min), and 1941 h (SD = 24 min), respectively. All of the three cortisol samples were found to be significantly and positively associated (r = 0.18 – 0.59, p < 0.05). The latent growth model with free time scores provided a good fit to the cortisol measures with χ2(13) = 12.5, p = 0.49, CFI = 1.00, RMSEA = 0.000, and SRMR = 0.024. The mean diurnal cortisol slope was estimated to be -4.93 nmol/L (SD = 1.74), which indicated an average decrease of 4.93 nmol/L in the diurnal cortisol levels. Waking cortisol was negatively and strongly 11
correlated with the diurnal slope (r = -0.65, p < 0.01). The mean cortisol level was 4.30 nmol/L and the AUC was 53.96 nmol/L-day. The diurnal slope was not significantly correlated with the mean cortisol level (r = 0.16, p = 0.10) and was positively correlated with the AUC (r = 0.22, p < 0.05).
3.3. Correlates of diurnal cortisol pattern at Time 1 The path analysis model provided an adequate fit with χ2(62) = 78.6, p = 0.08, CFI = 0.97, RMSEA = 0.042, SRMR = 0.053. Neither gender, time since psychiatric diagnosis, nor type of antipsychotic medication (Table 2) were significantly associated with the diurnal cortisol pattern (p > 0.05). Waking cortisol was negatively associated with perceived stress (β = -0.27, p < 0.01) and BMI (β = -0.40, p < 0.01). Diurnal cortisol slope was negatively associated with daily exercise span (β = -0.18, p < 0.05) and positively associated with perceived stress (β = 0.16, p < 0.05) and BMI (β = 0.37, p < 0.01). This implies that participants with lower perceived stress, lower BMI, and greater exercise level displayed a steeper (more normal) cortisol slope with greater decline throughout the day. The path model explained around one-fourth of the total variance of the diurnal cortisol patterns, denoting large effect sizes. [Table 2 about here]
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3.4. Prediction of outcome variables at Time 2 Reduced cortisol decline at Time 1 (Table 3) significantly predicted higher levels of positive symptoms (β = 0.25, p < 0.05), negative symptoms (β = 0.23, p < 0.01), motor deficit (β = 0.19, p < 0.05) and sequencing deficit (β = 0.18, p < 0.05) at Time 2. The diurnal cortisol pattern at Time 1 explained an additional R2 of 3.9%, 10.9%, 6.1%, 3%, and 1.8% for positive symptoms, negative symptoms, motor deficit, sequencing deficit, and daily functioning, respectively, suggesting small to moderate effect sizes. Figure 2 illustrates the statistically significant and positive relationships between the Time 1 diurnal cortisol slope and Time 2 symptom scores and neurological deficits. In particular, participants with reduced cortisol decline, i.e. less negative diurnal cortisol slope, displayed significantly higher levels of positive symptoms, negative symptoms, and neurological deficits at Time 2. Controlling for baseline status of the outcome variables at Time 1, females showed significantly higher levels of positive symptoms at Time 2 (β = 0.22, SE = 0.07, p < 0.01) and participants with higher BMI showed significantly lower levels of negative symptoms at Time 2 (β = -0.32, SE = 0.06, p < 0.01). Waking cortisol at Time 1 did not significantly predict any of the five outcome variables at Time 2 (p > 0.05). [Table 3 about here] [Figure 2 about here]
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4.
Discussion This study provided interesting findings on the associations between perceived stress
and diurnal cortisol patterns in patients with chronic schizophrenia. Higher levels of perceived stress and body-mass index and less physical activity were significantly linked to reduced cortisol decline. Reduced cortisol decline at Time 1 significantly predicted greater psychotic (positive and negative) symptoms and more severe neurological deficits in motor coordination and sequencing of complex motor acts at Time 2. In contrast to existing literature on elevations in cortisol release upon stress exposure (Walker et al., 2008), patients with greater perceived stress showed lower levels of waking baseline cortisol. Since the majority of the patients were currently receiving atypical antipsychotic treatment, this finding may be attributed to the suppression of the HPA axis activity caused by the antipsychotics, which led to reductions in the biological stress response. However, patients with greater perceived stress exhibited dysfunctional HPA axis activities in the form of reduced cortisol decline, lending partial support to our first research hypothesis. Controlling for the baseline status, chronicity, and type of antipsychotics, we did not find any significant associations between waking cortisol at Time 1 and the outcome variables at Time 2. Patients with reduced cortisol decline manifested greater psychiatric symptoms and neurological deficits. This result appears to be consistent with the neural diathesis–stress model (Walker et al., 2008) and support our second hypothesis. Dysfunctional HPA axis 14
activities, as indexed by reduced cortisol decline, have been associated with activation of dysfunctional dopamine pathways and greater symptom severity (Walder et al., 2000). Similarly, a recent study has linked HPA axis function abnormalities with poorer cognitive functioning among children at elevated risk for schizophrenia (Cullen et al., 2014). Taken together, these findings indicate abnormal HPA functioning in terms of poorer chronic response to daily stressors as denoted by the flatter cortisol slopes (failure to dampen during the day). The diurnal slope could be a more sensitive and appropriate measure of the HPA axis activity than the waking cortisol for patients with chronic schizophrenia. In contrast to recent findings on the lack of associations between salivary cortisol and obesity in a sample of 81 patients with early psychoses (Manzanares et al., 2014), patients with greater BMI and less daily exercise exhibited reduced cortisol decline in our study, supporting our third hypothesis. Such a discrepancy may be explained by the chronicity of the present sample and the current use of multiple cortisol assessments for a more precise reflection of the diurnal cortisol slope. It is worth noting that the majority of the present sample were classified as overweight (39.2%) or obese (18.8%) and two-fifths (40.9%) of them did not perform any exercise regularly. Although the weight gain plausibly reflects the side effects of antipsychotic treatments and intrinsic biological vulnerability (Baptista et al., 2004; Leucht et al., 2009), lifestyle factors such as poor dietary habits and reduced physical activity may be contributing factors (Dipasquale et al., 2013; Ratliff et al., 2012). 15
Given the associations of lifestyle factors with diurnal cortisol slopes, future interventions might focus on promoting healthy eating behavior to reduce intake of refined sugar and fat. Such practices together with regular exercise may help the patients maintain a normal BMI and improve their HPA axis functioning, which may lower the health risks of obesity and metabolic complications. Future studies are called for to corroborate the current findings and to elucidate the role of the HPA axis in mediating the effects of lifestyle factors on the study outcomes.
4.1. Limitations There are several limitations in this study. First, the findings of the present longitudinal study lend support to the neural diathesis–stress model. However, mutual interactions could probably exist among the HPA axis dysfunction and psychopathology. For instance, worsening psychotic symptoms and dysfunctions in HPA axis may induce greater subjective stress and this could further exacerbate the pathological process. Further studies with a cross-lagged design are needed for casual inference on the effects of the diurnal cortisol patterns on the variables and potential reciprocal effects. Second, the present findings are derived from a sample of patients with chronic schizophrenia (illness duration = 30 years). Cautions are warranted when generalizing the current results to other psychosis samples of shorter illness duration. In particular, further studies are encouraged to replicate these
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findings in first-episode or high-risk samples. Third, the collection times of the saliva samples were self-reported by the participants and may be subject to recall bias. Previous research (Kudielka et al., 2003) suggests that incorrect recording or sampling noncompliance may bias the diurnal cortisol slopes. Finally, the measurement scale for sequencing deficit showed unsatisfactory reliability (α < 0.60) and physical activity was measured based on a single item response. The lack of validated assessment scales with acceptable reliability might weaken the credibility of the results.
4.2. Conclusions The present study demonstrates that lower levels of BMI and perceived stress and a longer exercise span are associated with a favorable stress–endocrine response as indexed by steeper diurnal cortisol slopes in patients with chronic schizophrenia. Dysfunctional diurnal cortisol patterns at Time 1 significantly predicted greater psychotic symptoms and neurological deficits at Time 2. These results contribute to a better understanding of the diurnal cortisol patterns and their associations with the lifestyle factors, psychotic symptoms, and neurological deficits among the patients. Given the likely individual differences in the biobehavioral sequelae of HPA activity, person-centered mixture modeling methods (Muthen, 2001) could be adopted in future research to identify subgroups of patients who display intense symptom aggravations in response to elevations in cortisol secretion. Such findings
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would facilitate the development of an effective intervention program for high-risk subgroups of schizophrenic patients.
Figure legend: Figure 1. Conceptual model of the present study Figure 2. Relationship between diurnal cortisol slope and symptoms scores
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Table(s)
Table 1
Demographics and descriptive statistics of the sample (n = 149)
Variables
%
Gender Male / Female
54.1 / 45.9
Education level Primary / Secondary / Tertiary or above
40.0 / 53.1 / 6.9
Marital status Single / Married / Divorced
70.5 / 11.6 / 17.8
Antipsychotic medication Nil / Typical / Atypical
5.4 / 16.1 / 78.5 Mean ± SD
Age (in years)
54.1 ± 8.4
Duration of psychiatric diagnosis (in years)
29.9 ± 9.8
Body mass index (BMI) (in kg/m2)
24.0 ± 4.1
Daily exercise span (in minutes)
14.1 ± 15.4
Perceived stress (Time 1)
15.9 ± 6.6
Salivary cortisol (in nmol/L) Sample 1 (wake-up)
6.85 ± 4.12
Sample 2 (pre-lunchtime)
4.06 ± 2.82
Sample 3 (pre-bedtime)
1.88 ± 1.67
Positive symptoms (Time 1 / Time 2)
6.93 ± 3.63 / 7.40 ± 3.30
Negative symptoms (Time 1 / Time 2)
12.7 ± 5.6 / 12.8 ± 4.5
Motor deficit (Time 1 / Time 2)
4.85 ± 3.39 / 3.79 ± 3.03
Sequencing deficit (Time 1 / Time 2)
4.16 ± 1.72 / 3.48 ± 1.82
Activities of daily living (Time 1 / Time 2)
95.0 ± 7.8 / 97.0 ± 7.7
Table 2
Correlates of diurnal cortisol patterns at Time 1 Waking cortisol
Diurnal slope
β (SE)
β (SE)
Female
-0.03 (0.07)
-0.10 (0.08)
Time since psychiatric diagnosis
-0.12 (0.08)
0.12 (0.09)
Antipsychotic medication
0.09 (0.06)
-0.01 (0.07)
Perceived stress
-0.27 (0.07)**
0.16 (0.08)*
Body mass index
-0.40 (0.07)**
0.37 (0.07)**
0.10 (0.08)
-0.18 (0.07)*
0.27 (0.07)**
0.22 (0.06)**
Predictors
Daily exercise span R2 explained
* p < 0.05; ** p < 0.01; n = 149; β = standardized regression coefficient; SE = standard error.
Table 3
Regression analysis predicting T2 psychotic symptoms, neurological deficits and daily
functioning using T1 diurnal cortisol patterns Positive
Negative
Motor
Sequencing
Daily
symptoms
symptoms
deficit
deficit
functioning
β (SE)
β (SE)
β (SE)
β (SE)
β (SE)
Baseline status
0.34 (0.06)**
0.38 (0.05)**
0.36 (0.05)**
0.32 (0.05)**
0.32 (0.05)**
Waking cortisol
-0.01 (0.13)
-0.19 (0.10)
0.02 (0.09)
0.07 (0.08)
-0.11 (0.10)
Diurnal slope
0.25 (0.12)*
0.23 (0.08)**
0.19 (0.09)*
0.18 (0.09)*
-0.18 (0.12)
R2 explained
0.18 (0.05)**
0.31 (0.06)**
0.22 (0.07)**
0.15 (0.06)**
0.16 (0.07)*
Predictors
* p < 0.05; ** p < 0.01; n = 149; β: standardized regression coefficients; SE = standard errors.
Figure 1 Click here to download high resolution image
Figure 2 Click here to download high resolution image
*Acknowledgement
Acknowledgment: We would like to thank Mr. Joey Siu, Ms. Sharon Tam, and the staff of the Providence Garden for Rehab for their help with data collection and study coordination and Ms. Irene Cheung for coordinating the collection and laboratory analysis of the salivary cortisol data. This study was funded by the General Research Fund, Research Grants Council (GRF/HKU 744912).
*Conflict of Interest
Conflict of interest The authors declared that there is no conflict of interest related to this study.
*Contributors
Contributors Authors contributed to the manuscript as follows: Rainbow T. H. Ho designed and guided the study, supervised the writing of the manuscript, and revised the manuscript. Ted C. T. Fong undertook the literature searches, performed data analyses, and prepared the first draft of the manuscript. Adrian H. Y. Wan contributed to the implementation and data collection of the study and helped with pre-processing of the data. Friendly S. W. Au-Yeung contributed to the implementation of the study and recruitment of the patients and revised the manuscript. Eric Y. H. Chen critically reviewed and commented on the first draft of the manuscript. David Spiegel critically reviewed and commented on the first draft of the manuscript. All authors contributed to this study and approved the final manuscript.
*Role of the Funding Source
Role of the funding source This study was funded by the General Research Fund, Research Grants Council (GRF/HKU 744912). The Research Grants Council was not involved in study design, in the collection, analysis, and interpretation of data, in the writing of the article, or in the decision to submit the article for publication.
