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Distress and regional brain metabolism: a correlational study in metastatic breast cancer patients

Distress screening in cancer patients is internationally recommend as good practice in quality cancer care, since high levels of cancer-related distress may negatively impact on their clinical outcomes, such as survival and quality of life.
Distress involves a range of feelings from vulnerability and sadness to depression, anxiety, adjustment disorders, panic and isolation. As have been shown in studies done by a researcher of our team, Michael Antoni negative affect in breast cancer patients has been associated with flattened diurnal cortisol rhythmicity and dysfunction of immune functioning, namely greater leukocyte inflammatory gene (IL-1, IL-6, TNF) expression which are related to hypothalamic pituitary adrenal axis dysregulation (HPA). HPA dysregulation is relevant in mBC patients since alterations in circulating cortisol interacts with immune cells to upregulate inflammatory signaling, which could promote disease progression. Distress in cancer patients may also
be correlated with objective measures of changes (increase or decrease) in brain glucose metabolism, in regions within the limbic cortical circuit of the brain.
Distress can be measured through simple self-report instruments completed by the patient, which assess patients’ subjective experience. However in many centers and countries this is not yet standard clinical practice and as a consequence most of the psychological suffering in cancer patients goes unrecognized by the clinical staff and untreated. The identification of distress in cancer patients is an important target in clinical care for optimizing patients’ well-being and their outcomes. As such it would be important to have alternative ways in the existing routine clinical practice to detect it and, more important, to have a measure/indicator of patient propensity for distress in response to illness challenges. This study may give a contribution in this
Studies using positron emission tomography (PET) with non-cancer subjects have demonstrated correlations between depression assessed by self-report measures and alterations in regional cerebral glucose metabolism (rCGM), as well as regional cerebral perfusion/blood flow in some specific brain regions. However, no studies correlating distress (which does not necessarily involve depression) with rCGM in cancer patients have been reported. However, FDG-PET exams are used in clinical practice to assess disease progression and response to treatment in metastatic breast cancer patients (mBC). With this research project we aim to fill in this gap since our primary objective is to examine associations among individual differences in reported depression, anxiety, cortisol levels and rCGM measures (FDG-PET) of baseline activity in specific regions within the limbic-cortical circuit of the brain such as in the amygdala, pulvinar nucleus, dorsolateral prefrontal cortex and subgenual anterior cingulate cortex in mBC patients. We expect to find that increasing levels of distress will be related with increasing or decreasing rCGM measures (FDG-PET) in these same specific regions of the brain. This may allow us to identify one or more specific regions within the limbic-cortical circuit of the brain, which are sensitive to levels of heightened distress and HPA axis alterations and as such could serve as an objective indicator of patient’s affective style. Individual differences in tonic alterations of activity level in specific brain regions could predict differences in propensity for distress in response to illness challenges and therefore will have impact on clinical management of cancer patients facilitating proper and early referral for an adequate psychosocial preventive intervention.
Using this ‘smooth’ way of screening for distress included in a routine clinical exam would benefit patients and professionals and be cost-effective, as it would avoid using additional resources and patients’ time. Having selective ways to target patients’ propensity for distress in the cancer setting is an important objective. The positive impact to have such a measure is significant because it will allow: (1) early screening of patients at higher risk for psychological morbidity (mainly depression); (2) early referral for psychosocial care to prevent and/or reduce distress and psychological morbidity (3) optimize patients’ selection for psychosocial care to those who may benefit more and therefore optimize and reduce healthcare costs; (4) optimize clinical outcomes (by reducing the potential adverse effects in immune function produced by psychological distress and/or morbidity in cancer patients); (5) open the door to future work that can test whether people who receive anti-depressants or Cognitive Behavioral Therapy-based interventions will show objective changes in brain activity and (5) promote cancer care for the whole patient.