Fear of Fear and Broad Dimensions of Psychopathology over the Course of Cognitive Behavioural Therapy for Panic Disorder with Agoraphobia in Japan.

OBJECTIVE: To examine the relationship of fear of fear and broad dimensions of psychopathology in panic disorder with agoraphobia over the course of cognitive behavioural therapy in Japan. METHODS: A total of 177 Japanese patients with panic disorder with agoraphobia were treated with group cognitive behavioural therapy between 2001 and 2015. We examined associations between the change scores in Agoraphobic Cognitions Questionnaire or Body Sensations Questionnaire and the changes in subscales of Symptom Checklist-90 Revised during cognitive behavioural therapy controlling the change in panic disorder severity using multiple regression analysis. RESULTS: Reduction in Agoraphobic Cognitions Questionnaire score was related to a decrease in all Symptom Checklist-90 Revised (SCL-90-R) subscale scores. Reduction in Body Sensations Questionnaire score was associated with a decrease in anxiety. Reduction in Panic Disorder Severity Scale score was not related to any SCL-90-R subscale changes. CONCLUSIONS: Changes in fear of fear, especially maladaptive cognitions, may predict broad dimensions of psychopathology reductions in patients of panic disorder with agoraphobia over the course of cognitive behavioural therapy. For the sake of improving a broader range of psychiatric symptoms in patients of panic disorder with agoraphobia, more attention to maladaptive cognition changes during cognitive behavioural therapy is warranted.

History of diabetes and risk of suicide and accidental death in Japan: The Japan Public Health Centre-based Prospective Study, 1990-2012.

AIM: This study looked at whether a history of diabetes mellitus (DM) is associated with a higher risk of externally caused death (by suicide and accident), using data for a large population-based prospective cohort from an Asian population. METHODS: Data collected between 1990 and 2012 from the Japan Public Health Centre-based Prospective Study were analyzed, and Poisson regression models were used to calculate adjusted risk ratios (RR) for external causes of death. RESULTS: The population-based cohort comprised 105,408 Japanese residents (49,484 men and 55,924 women; mean age: 51.2 [SD 7.9] years). At baseline, 3250 (6.6%) men and 1648 (3.0%) women had a history of DM. During the follow-up period, 113 external deaths (41 suicides and 72 accidents) were noted among those with a history of DM, with 1304 external deaths (577 suicides and 727 accidents) among those without such a history. A higher risk of external death (men, RR: 1.4, 95% CI: 1.2-1.8; women, RR: 1.6, 95% CI: 1.01-2.4) was observed in those with a history of DM. Also, among those aged 40-49 years (RR: 1.9, 95% CI: 1.3-2.7) and 50-59 years (RR: 1.4, 95% CI: 1.05-1.9) at baseline, the risk of external death was significantly higher in those with a history of DM. CONCLUSION: Compared with people with no history of DM, those with such a history had a significantly greater risk of externally caused death (particularly accidental deaths) in both genders and in those aged≤59 years at baseline.

Clinical biopsychosocial risk factors for depression in lung cancer patients: a comprehensive analysis using data from the Lung Cancer Database Project.

BACKGROUND: Various risk factors for depression in lung cancer patients have been suggested but have been examined separately in studies with relatively small sample sizes. The present study examined the biopsychosocial risk factors of depression in lung cancer patients, focusing on psychological factors in the largest patient sample reported to date. PATIENTS AND METHODS: A total of 1334 consecutively recruited lung cancer patients were selected, and data on cancer-related variables, personal characteristics, health behaviors, physical symptoms, and psychological factors were obtained. The participants were divided into groups with or without depression using the Hospital Anxiety and Depression Scale. RESULTS: Among the recruited patients, 165 (12.4%) manifested depression. The results of a binary logistic regression analysis were significant (overall R2, 36.5%), and a greater risk for depression was strongly associated with psychological factors, such as personality characteristics (neuroticism) and coping style (low fighting spirit, helplessness/hopelessness, and anxious preoccupation). Although the contributions of cancer-related variables, personal characteristics, health behaviors, and clinical state were relatively low, cancer stage, cancer type, sex, and age correlated significantly with depression. CONCLUSION: Depression was most strongly linked with personality traits and coping style, and using screening instruments to identify these factors may be useful for preventive interventions.

Efficacy, tolerability and side-effect profile of fluvoxamine for major depression: meta-analysis.

Fluvoxamine, one of the oldest selective serotonin reuptaking inhibitors, is commonly prescribed to patients with major depression. Several studies have reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are outdated, have not been systematic and/or suffered from several methodological weaknesses. We conducted a systematic review to synthesize the best available evidence on the efficacy of fluvoxamine for adult patients suffering from major depression in comparison with other active antidepressive agents. Relevant randomized controlled trials were identified through a comprehensive search. The primary outcome was a relative risk of response, and the secondary outcome was a relative risk of remission. Tolerability and side-effect profile were also examined. Fifty-three trials were included. There were no large differences between fluvoxamine and any other antidepressants in terms of efficacy and tolerability. There is evidence of differing side effect profiles, especially when comparing gastrointestinal side effects between fluvoxamine and tricyclics. Clinicians should focus on practically or clinically relevant differences including those in side-effect profiles.

Psychotherapy for depression among incurable cancer patients.

BACKGROUND: The most common psychiatric diagnosis among cancer patients is depression; this diagnosis is even more common among patients with advanced cancer. Psychotherapy is a patient-preferred and promising strategy for treating depression among cancer patients. Several systematic reviews have investigated the effectiveness of psychological treatment for depression among cancer patients. However, the findings are conflicting, and no review has focused on depression among patients with incurable cancer. OBJECTIVES: To investigate the effects of psychotherapy for treating depression among patients with advanced cancer by conducting a systematic review of randomized controlled trials (RCTs). SEARCH STRATEGY: We searched the Cochrane Pain, Palliative and Supportive Care Group Register, The Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and PsycINFO databases in September 2005. SELECTION CRITERIA: All relevant RCTs comparing any kind of psychotherapy with conventional treatment for adult patients with advanced cancer were eligible for inclusion. Two independent review authors identified relevant studies. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the original reports using standardized data extraction forms. Two independent review authors also assessed the methodological quality of the selected studies according to the recommendations of a previous systematic review of psychological therapies for cancer patients that utilized ten internal validity indicators. The primary outcome was the standardized mean difference (SMD) of change between the baseline and immediate post-treatment scores. MAIN RESULTS: We identified a total of ten RCTs (total of 780 participants); data from six studies were used for meta-analyses (292 patients in the psychotherapy arm and 225 patients in the control arm). Among these six studies, four studies used supportive psychotherapy, one adopted cognitive behavioural therapy, and one adopted problem-solving therapy. When compared with treatment as usual, psychotherapy was associated with a significant decrease in depression score (SMD = -0.44, 95% confidence interval [CI] = -0.08 to -0.80). None of the studies focused on patients with clinically diagnosed depression. AUTHORS' CONCLUSIONS: Evidence from RCTs of moderate quality suggest that psychotherapy is useful for treating depressive states in advanced cancer patients. However, no evidence supports the effectiveness of psychotherapy for patients with clinically diagnosed depression.

Preferences regarding end-of-life cancer care and associations with good-death concepts: a population-based survey in Japan.

BACKGROUND: The aims of this study were to clarify end-of-life cancer care preferences and associations with good-death concepts. METHODS: The general population was sampled using a stratified random sampling method (N = 2548; response rate = 51%) and bereaved families from 12 certified palliative care units ('PCU-bereaved families') were surveyed (N = 513; response rate = 70%). The respondents reported their end-of-life care preferences and good-death concepts. RESULTS: Regarding place of end-of-life care, approximately 50% of the general population preferred 'Home', while 73% of PCU-bereaved families preferred 'PCU'. The concepts of 'Maintaining hope and pleasure' and 'Dying in a favorite place' were associated with the preference for 'Home'. Regarding prognostic disclosure, approximately 50% of the participants preferred some level of negotiation with the physician. The concept of 'Control over the future' was associated with this preference. Regarding treatment of severe refractory physical distress, 75% of the general population and 85% of the PCU-bereaved families preferred palliative sedation therapy. The concepts of 'Physical and psychological comfort' and 'Unawareness of death' were associated with this preference. CONCLUSIONS: End-of-life care preferences were associated with good-death concepts. It would be useful for health-care workers to discuss patients' good-death concepts to support subsequent treatment decisions.

Levels of omega-3 fatty acid in serum phospholipids and depression in patients with lung cancer.

Previous studies suggested that omega-3 fatty acids (FAs) have therapeutic effects against depression, but there is no evidence in the oncological setting. Our preliminary study reported the association between lower omega-3 FA intake and occurrence of depression in lung cancer patients. To explore the association further, the present study examined whether depression was associated with lower levels of omega-3 FAs in serum phospholipids. A total of 717 subjects in the Lung Cancer Database Project were divided into three groups by two cutoff points of the Hospital Anxiety and Depression Scale depression subscale (HADS-D). In all, 81 subjects of the nondepression and minor depression groups (HADS-D<5 and 510) for age, gender, clinical stage, and performance status. Fatty acids were assayed by gas chromatography and compared among the three matched groups. There were no differences between the major depression group and nondepression group in any FAs. The minor depression group had higher mean levels of docosahexaenoic acid (mean+/-s.d. (%), nondepression: 7.40+/-1.54; minor depression: 7.90+/-1.40; major depression: 7.25+/-1.52, P=0.017). These results suggested that serum FAs are associated with minor, but not major, depression in lung cancer patients.

Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies.

BACKGROUND: To explore the association between hydration volume and symptoms during the last 3 weeks of life in terminally ill cancer patients. PATIENTS AND METHODS: This was a multicenter, prospective, observational study of 226 consecutive terminally ill patients with abdominal malignancies. Primary responsible physicians and nurses evaluated the severity of membranous dehydration (dehydration score calculated from three physical findings), peripheral edema (edema score calculated from seven physical findings), ascites and pleural effusion (rated as physically undetectable to symptomatic), bronchial secretion, hyperactive delirium (Memorial Delirium Assessment Scale), communication capacity (Communication Capacity Scale), agitation (Agitation Distress Scale), myoclonus and bedsores. RESULTS: Patients were classified into two groups: the hydration group (n=59) who received 1 l or more of artificial hydration per day, 1 and 3 weeks before death, and the non-hydration group (n=167). The percentage of patients with deterioration in dehydration score in the final 3 weeks was significantly higher in the non-hydration group than the hydration group (35% versus 14%; P=0.002), while the percentages of patients whose symptom scores for edema, ascites and pleural effusion increased were significantly higher in the hydration group than the non-hydration group (44% versus 29%, P=0.039; 29% versus 8.4%, P <0.001; 15% versus 5.4%, P=0.016; respectively). After controlling for multiple covariates and treatment settings, the association between hydration group and dehydration/ascites score was statistically significant. Subgroup analysis of patients with peritoneal metastases identified statistically significant interaction between hydration group and dehydration/pleural effusion score. There were no significant differences in the degree of bronchial secretion, hyperactive delirium, communication capacity, agitation, myoclonus or bedsores. CONCLUSIONS: Artificial hydration therapy could alleviate membranous dehydration signs, but could worsen peripheral edema, ascites and pleural effusions. It is suggested that the potential benefits of artificial hydration therapy should be balanced with the risk of worsening fluid retention symptoms. Further clinical studies are strongly needed to identify the effects of artificial hydration therapy on overall patient well-being, and an individualized treatment and close monitoring of dehydration and fluid retention symptoms is strongly recommended.

Communication about the ending of anticancer treatment and transition to palliative care.

BACKGROUND: Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement. METHODS: A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%). RESULTS: Thirty-nine percent of the bereaved family members reported that they were 'very distressed' in receiving information about the ending of anticancer treatment, and 19% reported 'considerable' or 'much' improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions. CONCLUSIONS: In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer.

The aim of the present study was to examine the association between daily omega-3 fatty acid intake and depression in Japanese cancer patients. Omega-3 fatty acid intake in 771 patients with newly diagnosed primary lung cancer was evaluated using a food-frequency questionnaire, and the prevalence of depression was examined using the cutoff values for the depression subscale included in the Hospital Anxiety and Depression Scale. After adjustment for potential confounding factors, the odds ratio (OR) for depression among patients in the highest quartile of the total eicosapentaenoic acid- (C20:5n-3) and docosapentaenoic acid (C22:6n-3)-intake group compared with patients in the lowest quartile was not significantly different. On the other hand, the OR among the highest quartile of alpha-linolenic acid (C18:3n-3) intake (adjusted OR=0.50, 95% CI: 0.31-0.71, P for trend=0.004) and the highest quartile of total omega-3 fatty acid intake (adjusted OR=0.55, 95% CI: 0.35-0.88, P for trend=0.022) were significantly different. These results suggest that total eicosapentaenoic acid and docosapentaenoic acid intake might not be associated with depression in Japanese patients with newly diagnosed lung cancer, but that alpha-linolenic acid intake and total omega-3 fatty acid intake might be.

Psychiatric disorders and associated and predictive factors in patients with unresectable nonsmall cell lung carcinoma: a longitudinal study.

BACKGROUND: Few longitudinal studies have investigated psychiatric disorders in patients with unresectable nonsmall cell lung carcinoma (NSCLC). This study addressed three questions: 1) Which psychiatric disorders are prevalent among patients with unresectable NSCLC? 2) What is the clinical course of psychological distress? 3) Which factors are associated with this distress, and do any antecedent variables predict subsequent psychological distress? METHODS: A series of 129 consecutive patients with newly diagnosed, unresectable NSCLC participated. Psychiatric assessments were conducted by using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised between the time of diagnosis and initial treatment for NSCLC (baseline) and 6 months after diagnosis (follow-up). Potential associated and predictive variables, including sociodemographic, biomedical, and psychosocial factors, were explored. RESULTS: The most common psychiatric disorder at baseline was nicotine dependence (67%), followed by adjustment disorders (14%), alcohol dependence (13%), and major depression (5%). At follow-up, adjustment disorders were diagnosed in 16% of patients, and major depression was diagnosed in 3% of patients. Thirty-five percent of patients who experienced depressive disorders (adjustment disorders and/or major depression) at baseline continued to experience the same disorders at follow-up. Multivariate analysis revealed that relatively younger age and pain were associated significantly with psychological distress at baseline. Only self-reported anxiety and depression at baseline could predict subsequent psychological distress. CONCLUSIONS: Substance dependence and depressive disorders are common psychiatric disorders in patients with unresectable NSCLC. Although this form of malignant disease often is progressive, depressive disorders do not seem to increase during its clinical course. Pain management is essential for alleviating patients' depressive disorders, and self-rating depression and anxiety seems to be an indicator of subsequent depressive disorders.

Physician support and patient psychologic responses after surgery for nonsmall cell lung carcinoma: a prospective observational study.

BACKGROUND: In patients with cancer, depression and coping have been suggested to be important psychologic responses that may be associated with quality of life. Social support, especially from physicians, is considered important for cancer patients during their illness. The authors have investigated the impact of physician support on psychologic responses, including depression, psychologic distress and coping (such as fighting spirit and helplessness/hopelessness) in a cohort of patients with early-stage lung carcinoma. METHODS: After curative resection for nonsmall cell lung carcinoma, 226 patients were enrolled in a longitudinal study. The extent of social support, including physician support, was measured in structured interviews conducted 1 and 3 months after surgery. During the interviews, psychologic responses were measured using the Structured Clinical Interview for DSM-III-R, the Profiles of Mood States, and the Mental Adjustment to Cancer scale. Univariate and multivariate analyses were used to examine the impact of physician support on psychologic responses. RESULTS: Physician support had no effect on depression, but correlated negatively with psychologic distress (P < 0.05) and helplessness/hopelessness (P < 0.05), and positively with fighting spirit (P < 0.01). Multivariate analyses controlling for confounding biomedical and psychosocial variables revealed only physician support had a significant impact on fighting spirit, independently. However, this effect was limited to female patients or patients with no history of depression. CONCLUSION: In postoperative patients with nonsmall cell lung carcinoma, physician support may have a significant impact on fighting spirit, but this effect appears to be limited to female patients or patients with no history of depression.

Mental adjustment to first recurrence and correlated factors in patients with breast cancer.

Previous reports have demonstrated that breast cancer patients felt that news of their recurrence was more upsetting than their initial diagnosis. However, no studies have examined the factors that are correlated with mental adjustment in breast cancer patients who experienced recurrence. The authors investigated factors that are correlated with mental adjustment styles of fighting spirit or helplessness/hopelessness in women with breast cancer with a first recurrence. Fifty-five participants were interviewed and completed the Mental Adjustment to Cancer scale. Factors that correlated significantly with fighting spirit were performance status and history of major depression, while factors that correlated significantly with helplessness/hopelessness were age, pain, and history of major depression. These findings suggest that it is necessary to provide intervention for first recurrent breast cancer patients who have such biomedical factors, as young age, poor performance status, pain, and history of major depression to help them better cope with cancer.

Fatigue in ambulatory patients with advanced lung cancer: prevalence, correlated factors, and screening.

Although it has been indicated that patients with lung cancer experience higher level of fatigue than patients with other cancers, few published studies have focused on the characteristics of this fatigue and how it interferes with daily activities. The purpose of this study was to clarify fatigue prevalence and the factors correlated with fatigue, and to develop a screening method for fatigue in patients with advanced lung cancer. One hundred fifty-seven patients completed two fatigue scales (Cancer Fatigue Scale [CFS], and Fatigue Numerical Scale [FNS]) plus other measures, along with a self-administered questionnaire asking whether fatigue had interfered with any of 7 areas of daily activities. Fifty-nine percent of patients had experienced clinical fatigue, which was defined as fatigue that interfered with any daily activities. Logistic regression analysis demonstrated that symptoms of dyspnea on walking, appetite loss, and depression were significant correlated factors. Both CFS and FNS were found to have sufficient sensitivity and specificity for use as a screening tool. The results indicated that fatigue is a frequent and important symptom, which is associated with both physical and psychological distress in this population. The CFS and FNS were confirmed to have sufficient screening ability.

Psychiatric disorders in cancer patients: descriptive analysis of 1721 psychiatric referrals at two Japanese cancer center hospitals.

BACKGROUND: Although a diagnosis of cancer today may no longer be considered to be the equivalent of a death sentence, many previous studies in Western countries have revealed that such a diagnosis places many kinds of emotional burden on a patient. However, few studies have focused on the nature of psychiatric disorders in Japanese cancer patients. METHODS: We investigated the characteristics, reason for psychiatric consultation and psychiatric diagnosis of cancer patients by analyzing the database of patients referred to the Psychiatry Divisions at the National Cancer Center Hospital and the National Cancer Center Hospital East, Japan. RESULTS: Among a total of 1721 referrals, most of the cancer patients (78%) were inpatients. Patients with lung cancer (19%) were the most common, followed by patients with breast cancer (13%) and with head and neck cancer (10%). More than half of the patients had recurrent and/or metastatic cancer and 60% of the patients had pain. The most common reason for the consultation was psychiatric evaluation (35%), followed by sleep disorders (19%), anxiety or fear (18%) and depression (18%). Regarding the psychiatric diagnosis, adjustment disorders were the most common (34%), followed by delirium (17%) and major depression (14%). The diagnosis of cancer had been disclosed to more than 99% of the patients. CONCLUSION: The common psychiatric disorders observed in Japanese cancer patients were similar to those in the Western countries provided the cancer diagnosis is disclosed.

[Psycho-oncology and its scientific background].

Psycho-oncology has two purposes corresponding to the psychosocial aspects of cancer: 1. to clarify the psychosocial impacts of cancer on the quality of life of the patient, family and staff; 2. to clarify the role that psychosocial and behavioral variables may have in cancer risk and survival. For these purposes, patient education, counseling, behavioral and psychopharmacological techniques have been applied to clinical oncology. In this paper, we review psycho-oncology and its scientific background, with respect to neuroradiology and molecular genetics, as well as psychiatry, psychology, epidemiology, pharmacology and immunology.

Biomedical and psychosocial determinants of psychiatric morbidity among postoperative ambulatory breast cancer patients.

There has been much interest in the psychosocial issues faced by breast cancer patients because of the high prevalence of the disease and the severe psychological impact of the cancer itself, as well as its treatment. The objective of our study was to investigate the determinants of psychiatric morbidity among postoperative ambulatory breast cancer patients. The variables examined included the patients' biomedical characteristics, demographic characteristics, current concerns, coping responses and social support factors. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Mental Adjustment to Cancer scale (MAC scale), and information pertaining to demographic variables, current concerns and social support factors was obtained by a specially designed questionnaire. Available data were obtained from 148 randomly selected postoperative ambulatory breast cancer patients. The prevalence of psychiatric morbidity (including clinical anxiety and depression) evaluated by using the HADS cut-off point was 23%. The results of univariate analyses indicated that pain, dyspnea, having children with health problems, various other concerns (about children, other family members, the patients' own health and future treatment) and poor coping responses (low fighting spirit, high anxious preoccupation, high fatalism and high helplessness/hopelessness) were significant determinants of the patients' psychiatric morbidity. Additionally, in the logistic regression analysis, having children with health problems and having a low fighting spirit and a high helplessness/hopelessness were final significant determinants. Postoperative ambulatory breast cancer patients with these problems should be given careful attention, and psychosocial intervention may be beneficial for them.

Why do some cancer patients with depression desire an early death and others do not?

Major depression is a well-documented risk factor for suicide in cancer patients as well as in the general population. However, there are no data explaining why some cancer patients suffering from major depression have suicidal ideation, while others do not. The authors investigated the background differences among cancer patients suffering from major depression with and without suicidal ideation by analyzing the consultation data of patients referred to the psychiatry division. Among the 1,721 referred patients, 220 (12.8%) were diagnosed with major depression, and of these 113 (51.4%) had suicidal ideation. Logistic regression analysis indicated that poor physical functioning and severe depression were significant risk factors. These preliminary findings suggest that the severity of major depression and physical functioning are important indicators of suicidal ideation among cancer patients.

Three sets of diagnostic criteria for major depression and correlations with serotonin-induced platelet calcium mobilization in cancer patients.

OBJECTIVE: Enhanced serotonin-induced platelet calcium mobilization has been proposed to be a biological marker for the pathophysiology of major depression in physically healthy patients. To determine the most appropriate method of diagnosing major depression in cancer patients, we compared serotonin-induced platelet calcium mobilization between patients with and without major depression diagnosed according to three different sets of diagnostic criteria (inclusive, substitutive and exclusive). METHODS: Among the cancer patients referred to our institution between June 1997 and March 1998, 24 patients diagnosed as having major depression according to the inclusive approach (in which the nine traditional symptoms of major depression contribute towards the diagnosis of depression regardless of its presumed etiology) participated in the study. Serotonininduced platelet calcium mobilization was examined in these patients and in the same number of non-depressed controls matched for age, sex, cancer stage and cancer site. The depressed patients were then re-evaluated using substitutive and exclusive criteria, and calcium mobilization comparisons with the relevant controls were repeated. RESULTS: Compared with the controls, an enhanced serotonin-induced platelet calcium response was only observed in the patients with major depression according to the exclusive criteria. No significant enhancement was observed when the inclusive or substitutive approaches were used. CONCLUSION: These findings, based on the use of enhanced serotonin-induced platelet calcium mobilization as a biological marker, suggest that the exclusive approach might be the most valid and appropriate method of diagnosing major depression in cancer patients, while the inclusive and substitutive approaches might overestimate the occurrence of major depression in these patients.