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1.  Alcohol use in the first three years of bereavement: a national representative survey 
Earlier results concerning alcohol consumption of bereaved persons are contradictory. The aim of the present study was to analyze the relationship between bereavement and alcohol consumption accounting for time and gender differences on a nationally representative sample from Hungary ("Hungarostudy Epidemiological Panel Survey", N = 4457)
Drinking characteristics of mourning persons (alcohol consumption, dependence symptoms, and harmful consequences of alcohol use) in the first three years of grief were examined among persons between 18-75 years using the Alcohol Use Disorders Identification Test (AUDIT).
Men bereaved for one year scored higher on two dimensions of AUDIT (dependence symptoms and harmful alcohol use), while men bereaved for two years scored higher on all three dimensions of AUDIT compared to the non-bereaved. The rate of men clinically at-risk concerning alcohol consumption among the non-bereaved is 12.9%, and among men bereaved for one year is 18.4% (a non-significant difference), while 29.8% (p < 0.001, OR = 2,781) among men bereaved for two years. However, men bereaved for three years did not differ from the non-bereaved in their drinking habits. In case of bereaved women, again no difference was found with respect to alcohol use compared to the non-bereaved.
Among bereaved men, the risk of alcohol related problems tends to be higher, which can be shown both among men bereaved for one year as well as men bereaved for two years. Considering the higher morbidity and mortality rates of bereaved men, alcohol consumption might play a mediator role. These facts draw attention to the importance of prevention, early recognition, and effective therapy of hazardous drinking in bereaved men.
PMCID: PMC3286419  PMID: 22248360
bereavement; alcohol consumption; national representative survey; gender differences
2.  Bereavement reduces neutrophil oxidative burst only in older adults: role of the HPA axis and immunesenescence 
The effect of the chronic stress of bereavement on immunity is poorly understood. Previous studies have demonstrated negative effects on immunity in older adults, and those who report higher depressive symptoms. The aim of the present study was to compare the effect of bereavement on neutrophil function in healthy young and old adults, also assessing serum levels of the stress hormones, cortisol and dehydroepiandrosterone sulphate (DHEAS). 41 young (mean age 32 years) and 52 older adults (mean age 72 years), bereaved and non-bereaved, took part in the study. They completed questionnaires on socio-demographic and health behaviour characteristics, as well as psychosocial variables, and provided a blood sample for analysis of neutrophil function (phagocytosis and reactive oxygen species (ROS) production) and stress hormone analysis.
Bereaved participants in both age groups reported more symptoms of depression and anxiety than controls and scored moderately highly on bereavement-specific questionnaires for these symptoms. Despite this, young bereaved participants showed robust neutrophil function when compared to age-matched non-bereaved controls, and comparable stress hormone levels, while reduced neutrophil ROS production and raised stress hormone levels (cortisol:DHEAS ratio) were seen in the older bereaved group compared to their age-matched controls.
Reduced neutrophil function among older bereaved participants may be the result of the inability to maintain stress hormone balance, specifically the cortisol:DHEAS ratio.
PMCID: PMC4154898  PMID: 25191511
Bereavement; Neutrophil function; Cortisol; DHEAS; Social support
3.  Bereavement Related and Non-Bereavement Related Depressions: A Comparative Field Study 
Journal of affective disorders  2008;112(1-3):102-110.
In the otherwise atheoretical diagnostic manual, the DSM-III and IV bereavement exclusion for the diagnosis of major depression (MDD) stands out as the sole exception to the rule. No other life event excludes the diagnosis of any other axis I disorder. Since this diagnostic convention has important diagnostic and treatment implications, it is important to evaluate the validity of this exception. By comparing multiple features of bereavement related to non-bereavement related MDD, this prospective community study critically evaluates the validity of the bereavement exclusion
The prevalence of conditional criteria was common in the total sample (N=685) and did not differ between bereaved and non-bereaved groups. The global ‘symptom profile’ of depressed individuals was similar in both groups. ‘Duration’ was found to be longer in the bereaved group. Among all conditional criteria required by DSM-IV to accept bereavement related episodes under the category of MDD, only ‘marked dysfunction’ predicted treatment. Neither the ‘four conditional symptoms’ nor the ‘duration’ criterion predicted marked dysfunction. The ‘risk for recurrence’ was similar whether the first episode was bereavement related or not.
‘Psychotic symptoms’ were not assessed, and ‘marked dysfunction’ was not assessed on a continuous scale. The number of DSM-IV excluded episodes was too small to allow for generalization.
Our results suggest that the conditional criteria do not seem to serve the purpose of the originators of the bereavement exclusion criteria. The ‘conditional symptoms’ and the ‘duration’ criterion seem not to be markers of severity. We propose that the descriptive and etiologically neutral approach the DSM presumes in reaching a diagnosis should be applied in the case of MDD until more convincing data point to the contrary.
PMCID: PMC2648140  PMID: 18514321
bereavement; depression; conditional criteria; DSM
4.  Mortality after Parental Death in Childhood: A Nationwide Cohort Study from Three Nordic Countries 
PLoS Medicine  2014;11(7):e1001679.
Jiong Li and colleagues examine mortality rates in children who lost a parent before 18 years old compared with those who did not using population-based data from Denmark, Sweden, and Finland.
Please see later in the article for the Editors' Summary
Bereavement by spousal death and child death in adulthood has been shown to lead to an increased risk of mortality. Maternal death in infancy or parental death in early childhood may have an impact on mortality but evidence has been limited to short-term or selected causes of death. Little is known about long-term or cause-specific mortality after parental death in childhood.
Methods and Findings
This cohort study included all persons born in Denmark from 1968 to 2008 (n = 2,789,807) and in Sweden from 1973 to 2006 (n = 3,380,301), and a random sample of 89.3% of all born in Finland from 1987 to 2007 (n = 1,131,905). A total of 189,094 persons were included in the exposed cohort when they lost a parent before 18 years old. Log-linear Poisson regression was used to estimate mortality rate ratio (MRR). Parental death was associated with a 50% increased all-cause mortality (MRR = 1.50, 95% CI 1.43–1.58). The risks were increased for most specific cause groups and the highest MRRs were observed when the cause of child death and the cause of parental death were in the same category. Parental unnatural death was associated with a higher mortality risk (MRR = 1.84, 95% CI 1.71–2.00) than parental natural death (MRR = 1.33, 95% CI 1.24–1.41). The magnitude of the associations varied according to type of death and age at bereavement over different follow-up periods. The main limitation of the study is the lack of data on post-bereavement information on the quality of the parent-child relationship, lifestyles, and common physical environment.
Parental death in childhood or adolescence is associated with increased all-cause mortality into early adulthood. Since an increased mortality reflects both genetic susceptibility and long-term impacts of parental death on health and social well-being, our findings have implications in clinical responses and public health strategies.
Please see later in the article for the Editors' Summary
Editors' Summary
When someone close dies, it is normal to grieve, to mourn the loss of that individual. Initially, people who have lost a loved one often feel numb and disorientated and find it hard to grasp what has happened. Later, people may feel angry or guilty, and may be overwhelmed by feelings of sadness and despair. They may become depressed or anxious and may even feel suicidal. People who are grieving can also have physical reactions to their loss such as sleep problems, changes in appetite, and illness. How long bereavement—the period of grief and mourning after a death—lasts and how badly it affects an individual depends on the relationship between the individual and the deceased person, on whether the death was expected, and on how much support the mourner receives from relatives, friends, and professionals.
Why Was This Study Done?
The loss of a life-partner or of a child is associated with an increased risk of death (mortality), and there is also some evidence that the death of a parent during childhood leads to an increased mortality risk in the short term. However, little is known about the long-term impact on mortality of early parental loss or whether the impact varies with the type of death—a natural death from illness or an unnatural death from external causes such as an accident—or with the specific cause of death. A better understanding of the impact of early bereavement on mortality is needed to ensure that bereaved children receive appropriate health and social support after a parent's death. Here, the researchers undertake a nationwide cohort study in three Nordic countries to investigate long-term and cause-specific mortality after parental death in childhood. A cohort study compares the occurrence of an event (here, death) in a group of individuals who have been exposed to a particular variable (here, early parental loss) with the occurrence of the same event in an unexposed cohort.
What Did the Researchers Do and Find?
The researchers obtained data on everyone born in Denmark from 1968 to 2008 and in Sweden from 1973 to 2006, and on most people born in Finland from 1987 to 2007 (more than 7 million individuals in total) from national registries. They identified 189,094 individuals who had lost a parent between the age of 6 months and 18 years. They then estimated the mortality rate ratio (MRR) associated with parental death during childhood or adolescence by comparing the number of deaths in this exposed cohort (after excluding children who died on the same day as a parent or shortly after from the same cause) and in the unexposed cohort. Compared with the unexposed cohort, the exposed cohort had 50% higher all-cause mortality (MRR = 1.50). The risk of mortality in the exposed cohort was increased for most major categories of cause of death but the highest MRRs were seen when the cause of death in children, adolescents, and young adults during follow-up and the cause of parental death were in the same category. Notably, parental unnatural death was associated with a higher mortality risk (MRR = 1.84) than parental natural death (MRR = 1.33). Finally, the exposed cohort had increased all-cause MRRs well into early adulthood irrespective of child age at parental death, and the magnitude of MRRs differed by child age at parental death and by type of death.
What Do These Findings Mean?
These findings show that in three high-income Nordic countries parental death during childhood and adolescence is associated with an increased risk of all-cause mortality into early adulthood, irrespective of sex and age at bereavement and after accounting for baseline characteristics such as socioeconomic status. Part of this association may be due to “confounding” factors—the people who lost a parent during childhood may have shared other unknown characteristics that increased their risk of death. Because the study was undertaken in high-income countries, these findings are unlikely to be the result of a lack of material or health care needs. Rather, the increased mortality among the exposed group reflects both genetic susceptibility and the long-term impacts of parental death on health and social well-being. Given that increased mortality probably only represents the tip of the iceberg of the adverse effects of early bereavement, these findings highlight the need to provide long-term health and social support to bereaved children.
Additional Information
Please access these websites via the online version of this summary at
The UK National Health Service Choices website provides information about bereavement, including personal stories; it also provides information about children and bereavement and about young people and bereavement, including links to not-for-profit organizations that support children through bereavement
The US National Cancer Institute has detailed information about dealing with bereavement for the public and for health professionals that includes a section on children and grief (in English and Spanish)
The US National Alliance for Grieving Children promotes awareness of the needs of children and teens grieving a death and provides education and resources for anyone who wants to support them
MedlinePlus provides links to other resources about bereavement (in English and Spanish)
PMCID: PMC4106717  PMID: 25051501
5.  Grief, Depressive Symptoms, and Physical Health Among Recently Bereaved Spouses 
The Gerontologist  2011;52(4):460-471.
Purpose: Widowhood is among the most distressing of all life events, resulting in both mental and physical health declines. This paper explores the dynamic relationship between physical health and psychological well-being among recently bereaved spouses. Design and Methods: Using a sample of 328 bereaved persons who participated in the “Living After Loss” study, we modeled trends in physical health, somatic symptoms, and psychological well-being over the first year and a half of widowhood. The primary focus is whether physical health at the time of widowhood modifies psychological well-being over time. Results: There were considerable somatic symptoms during the earliest months of bereavement but no major health declines over the first year and half of bereavement. Those in poor health had initially higher levels of grief and depressive symptoms, but the trajectories or changes over time were similar regardless of health status. Those with poor health at the time of widowhood had significantly higher risks of complicated grief and major depression disorder. Implications: Bereavement requires physical and emotional adjustment, but the psychological trajectory of bereavement may be somewhat universal. Bereavement support ought to include a focus on self-care and health promotion in addition to emotional support, especially because those with poor health initially may be most susceptible to prolonged and intense clinical distress.
PMCID: PMC3391379  PMID: 22156713
Bereavement; Depression; Health; Widowhood; Growth curve modeling; Grief
Depression and anxiety  2013;30(12):1211-1216.
Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD.
Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of ≥30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively.
Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher’s Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (β = −0.140, P = 0.023) and greater impairment (β = 0.141, P = 0.035) among individuals with AD.
Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted.
PMCID: PMC4038035  PMID: 23495105
Complicated grief; grief; bereavement; anxiety; comorbidity; quality of life
7.  The Unique Impact of Late-Life Bereavement and Prolonged Grief on Diurnal Cortisol 
This study expands on previous research by examining the effects of prolonged grief disorder (PGD) symptoms and bereavement on diurnal cortisol patterns above and beyond depressive symptomatology.
Drawing on information from 56 depressed older adults, 3 groups were compared: (1) a depressed nonbereaved group, (2) a depressed bereaved without elevated PGD symptoms group, and (3) a depressed bereaved with elevated PGD symptoms group. Multilevel modeling was used to examine differences in diurnal cortisol profiles between these 3 groups, controlling for demographic factors and depressive symptoms.
Results revealed that those who were bereaved had more dysregulated cortisol patterns, but PGD symptomatology seemed to have little effect. Subsidiary analysis with just the bereaved participants suggests that those who were recently widowed may have had greater cortisol dysregulation compared with other bereaved individuals in the sample.
These findings suggest that the circumstance of being bereaved may be associated with more dysregulated cortisol, regardless of PGD symptomatology. This pattern of results might reflect greater disturbance in daily routines among bereaved individuals and acute stress in the case of those experiencing the recent loss of a spouse, which leads to disruption in circadian rhythms and the diurnal cycle of cortisol.
PMCID: PMC3894130  PMID: 23740094
Biomarkers; Death and dying; Widowhood; Salivary cortisol; Complicated grief.
8.  Psychiatric Symptoms in Bereaved versus Non-Bereaved Youth and Young Adults: A Longitudinal Epidemiological Study 
To examine potential differences in psychiatric symptoms between parent-bereaved youth (N=172), youth who experienced the death of another relative (N=815), and non-bereaved youth (N=235), aged 11 to 21, above and beyond antecedent environmental and individual risk factors.
Socio-demographics, family composition, and family functioning were assessed one interview wave prior to the death. Child psychiatric symptoms were assessed during the wave in which the death was reported and one wave before and after the death. A year was selected randomly for the non-bereaved group.
The early loss of a parent was associated with poverty, previous substance abuse problems, and greater functional impairment before the loss. Both bereaved groups of children were more likely than non-bereaved children to show symptoms of separation anxiety and depression during the wave of the death, controlling for socio-demographic factors and prior psychiatric symptoms. One wave following the loss, bereaved children were more likely than non-bereaved children to exhibit symptoms of conduct disorder and substance abuse and to show greater functional impairment.
The impact of parental death on children must be considered in the context of pre-existing risk factors. Even after controlling for antecedent risk factors, both parent-bereaved children as well as those who lost other relatives were at increased risk for psychological and behavioral health problems.
PMCID: PMC2965565  PMID: 20970702
Bereavement; Children; Psychiatric Symptoms; Longitudinal; Epidemiological
9.  Psychosomatic Status, Personality Traits, and Coping Styles of Bereaved and Non-Bereaved Survivors of the 2008 Wenchuan Earthquake, China 
This study examined personality, coping styles, and psychosomatic characteristics and their relationships in bereaved and non-bereaved earthquake survivors.
Study design
Cross-sectional survey.
A survey was conducted with a sample of 102 non-bereaved survivors and 79 bereaved survivors from Mianyang, Anyang, and similar districts 2 weeks after Wenchuan earthquake. Survivors completed questionnaires, including items about demographics, personality characteristics, coping styles, and psychosomatic status.
Bereaved survivors had lower scores for gregariousness, trust, and optimism, but higher scores for depressed mood, loneliness, becoming easily fearful, irritation, and anxiety than non-bereaved survivors. In addition, bereaved participants scored higher for avoiding problems, self-blame, and fantasy coping styles than non-bereaved ones. Personality and coping styles significantly correlated with psychosomatic status in bereaved and non-bereaved survivors. Optimism and openness to feelings personality characteristics, and self-blame, avoiding problems, and rationalization coping styles significantly predicted psychosomatic status of bereaved survivors, whereas openness to fantasy, optimism, order, and trust personality characteristics, and self-blame and avoiding problems coping styles significantly predicted psychosomatic status of non-bereaved survivors.
Earthquake survivors experienced post-traumatic stress disorder (PTSD) symptoms and negative emotions. Bereaved survivors experienced more serious PTSD symptoms and negative emotions relative to non-bereaved survivors. Appropriate psychological crisis interventions should be conducted for earthquake survivors, especially bereaved survivors.
PMCID: PMC4786572  PMID: 27014096
personality; coping; psychosomatic status; bereaved survivors; Wenchuan earthquake
10.  War and Bereavement: Consequences for Mental and Physical Distress 
PLoS ONE  2011;6(7):e22140.
Little is known about the long-term impact of the killing of a parent in childhood or adolescence during war on distress and disability in young adulthood. This study assessed current prevalence rates of mental disorders and levels of dysfunction among young adults who had lost their father due to war-related violence in childhood or adolescence.
179 bereaved young adults and 175 non-bereaved young adults were interviewed a decade after experiencing the war in Kosovo. Prevalence rates of Major Depressive Episode (MDE), anxiety, and substance use disorders, and current suicide risk were assessed using the Mini–International Neuropsychiatric Interview. The syndrome of Prolonged Grief Disorder (PGD) was assessed with the Prolonged Grief Disorder Interview (PG-13). Somatic symptoms were measured with the Patient Health Questionnaire. General health distress was assessed with the General Health Questionnaire.
Bereaved participants were significantly more likely to suffer from either MDE or any anxiety disorder than non-bereaved participants (58.7% vs. 40%). Among bereaved participants, 39.7% met criteria for Post-Traumatic Stress Disorder, 34.6% for PGD, and 22.3% for MDE. Bereaved participants with PGD were more likely to suffer from MDE, any anxiety disorder, or current suicide risk than bereaved participants without PGD. Furthermore, these participants reported significantly greater physical distress than bereaved participants without PGD.
War-related loss during middle childhood and adolescence presents significant risk for adverse mental health and dysfunction in young adulthood in addition to exposure to other war-related traumatic events. Furthermore, the syndrome of PGD can help to identify those with the greatest degree of distress and dysfunction.
PMCID: PMC3134481  PMID: 21765944
11.  Stillbirth as risk factor for depression and anxiety in the subsequent pregnancy: cohort study 
BMJ : British Medical Journal  1999;318(7200):1721-1724.
To assess women’s symptoms of depression and anxiety during pregnancy and the postpartum year in the pregnancy after stillbirth; to assess relevance of time since loss.
Cohort study with four assessments: in third trimester and 6 weeks, 6 months, and 12 months after birth.
Outpatient departments of three district general hospitals; subjects’ homes.
60 women whose previous pregnancy ended in stillbirth after 18 weeks’ gestation; 60 matched controls.
Main outcome measures
Depression and anxiety measured by Edinburgh postnatal depression scale, Beck depression inventory, and Spielberger state-trait anxiety scale.
In the third trimester women whose previous pregnancy had ended in stillbirth were significantly more depressed than control women (10.8 v 8.2; P=0.004) and had greater state anxiety (39.8 v 32.8, P=0.003) The difference was accounted for by those women who conceived less than 12 months after the stillbirth, who were also more depressed at 1 year. Results in those who conceived 12 months or more after stillbirth were similar to those in their controls at all points and showed lower trait anxiety 1 year post partum. One year after the birth 8% of control women and 19% of subjects scored high for depression (P=0.39), with most of the depression among the more recently bereaved (28% v 11%; P=0.18). In the women who had experienced stillbirth, depression in the third trimester was highly predictive of depression 1 year after subsequent birth (P⩽0.0005).
Vulnerability to depression and anxiety in the next pregnancy and puerperium is related to time since stillbirth, with more recently bereaved women at significantly greater risk than controls. As there are problems for mother and infant associated with high anxiety and depression during and after pregnancy, there may be advantage in waiting 12 months before the next conception.
Key messagesWomen whose previous pregnancy ended in stillbirth had significantly higher levels of depression and state anxiety during their subsequent pregnancy than matched controlsThose who had conceived over 12 months after stillbirth were, however, similar to controls at all points and had lower trait anxiety a year after the next birthWomen who had conceived within 12 months after loss had a significantly higher risk of high state anxiety during the next pregnancy and of depression and both state and trait anxiety 12 months post partum than women with longer time since lossWomen may need a year to mourn the lost child before beginning another pregnancy or women who chose to conceive sooner may be intrinsically more vulnerable to depression and anxietyParents have various and individual reasons for timing the next pregnancy, but there may be advantage in waiting 12 months before conception
PMCID: PMC31099  PMID: 10381705
12.  Health care utilization, somatic and mental health distress, and well-being among widowed and non-widowed female survivors of war 
BMC Psychiatry  2012;12:39.
The aim of the study was to assess levels of somatic and mental health distress, well-being, AS WELL AS utilization of primary and specialist health care services among war-related widowed and non-widowed female civilian survivors of war.
100 war-related widowed lone mothers and 106 non-widowed mothers who had experienced the Kosovo war ten years previously participated in the study. Measures of somatic, depressive, post-traumatic stress, anxiety, and grief complaints, subjective well-being, and utilization of health care services during the previous three months were used.
Compared to non-widowed mothers, widowed lone mothers reported significantly higher levels of somatic, depressive, post-traumatic stress, and anxiety complaints. Further, they reported significantly lower levels of subjective well-being as composed of positive and negative affect and satisfaction with life. More than half of both widowed and non-widowed mothers reported utilization of health care services during the last three months, without significant differences between the groups. However, only three percent of widowed lone mothers and four percent of non-bereaved mothers reported utilization of mental health services during the last three months, despite high levels of mental health distress especially among widowed lone mothers. Among widowed lone mothers, severity of prolonged grief symptoms significantly predicted number of contacts of specialist health care use over and above sociodemographic variables, number of war-related events, and other psychopathology.
War-related widowed lone mothers suffer from elevated somatic and mental distress even a decade after the war. The tiny proportion of widowed lone mothers in use of mental health services can be seen as a reflection of lack of previous and current mental health services to meet mental health needs of this population.
PMCID: PMC3418153  PMID: 22578096
Although bereavement and depression are both common in older primary care patients, the effect of bereavement on depression intervention outcomes is unknown. We examined whether standard interventions for depression in primary care were as effective for bereaved as for non-bereaved depressed patients.
Randomized controlled trial.
Twenty community-based primary care practices in New York and greater Philadelphia and Pittsburgh. Randomization to either Intervention or Usual Care occurred by practice.
Patients ≥ 60 who met criteria for major depression or clinically significant minor depression (N=599). Patients who did not complete the bereavement measure or who were missing 4-month data were excluded (final N=417).
Study-trained depression care managers offered guideline concordant recommendations to primary care physicians at intervention sites and assisted patients with treatment adherence. Patients who did not wish to take antidepressants could receive interpersonal psychotherapy.
Bereavement was captured using the Louisville Older Persons Events Schedule (LOPES). Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HDRS). Outcomes at 4 months were remission (HDRS ≤7) and response (HDRS reduction ≥50% from baseline).
Logistic regressions indicated that, for non-bereaved participants, response and remission were higher in Intervention than Usual Care. However, recently bereaved older adults were less likely to achieve response or remission at 4 months if treated in the Intervention Condition.
Standard depression care management appears to be ineffective among recently bereaved older primary care patients. Greater attention should be paid in primary care to emotional distress in the context of bereavement.
PMCID: PMC4057992  PMID: 24418366
depression; bereavement; case management; primary care; clinical trial
14.  Bereavement and the Diagnosis of Major Depressive Episode 
Bereavement-related depression is excluded from a diagnosis of major depressive episode (MDE) in DSM-IV unless the syndrome is prolonged or complicated. The objective of this study is to assess the validity of the bereavement exclusion by comparing characteristics of bereavement-related episodes that are excluded from a diagnosis, and bereavement-related episodes that qualify for a diagnosis (complicated bereavement), to MDE.
We used data from two waves of the National Epidemiologic Survey on Alcohol and Related Conditions to compare bereavement-excluded depression and complicated bereavement to MDE with respect to indicators of pre-existing risk for psychopathology (antecedent indicators) and indicators of disorder severity (consequent indicators).
Compared to individuals with MDE, individuals with bereavement-excluded depression had lower risks of pre-existing psychiatric disorders (e.g., 0.44 lower odds of social phobia, P=0.006), fewer depressive episodes (recurrence rate 0.37 times lower, P<0.001), less impairment, an 0.18 times lower odds of seeking treatment (P<0.001), and a lower risk of psychiatric disorders during a 3-year follow-up period. Unexpectedly, this same pattern of differences was observed between individuals with complicated bereavement and MDE.
Despite the presence of a clinically significant depressive episode, bereavement-excluded depression is in many ways less indicative of psychopathology than MDE. However, complicated bereavement was more similar to bereavement-excluded depression than to MDE. We therefore question whether the DSM-IV criteria validly distinguish between non-disordered loss reactions (bereavement-excluded depression), pathological loss reactions (complicated bereavement), and non-loss related MDE.
PMCID: PMC3721753  PMID: 21903020
Depression; bereavement; validity
15.  Psychological morbidity among suicide-bereaved and non-bereaved parents: a nationwide population survey 
BMJ Open  2013;3(8):e003108.
To determine how psychological premorbidity affects the risk of depression in parents who lost a child through suicide.
Population-based survey.
Sweden, between 2009 and 2010.
All parents who lost a child, age 15–30, through suicide between 2004 and 2007 according to National population registries. Non-bereaved parents matched for age, sex, living area, marital status, number of children. Exclusion criteria: born outside a Nordic country, not Swedish speaking, contact details missing. Participants: 666 of 915 (73%) suicide-bereaved and 377 of 508 (74%) non-bereaved parents.
Main outcome measures
Depression measured by the nine-item depression scale of the Patient Health Questionnaire (PHQ-9) and study-specific questions to assess psychological premorbidity and experience of the child's presuicidal morbidity.
In all, 94 (14%) suicide-bereaved and 51 (14%) non-bereaved parents (relative risk 1.0; 95% CI 0.8 to 1.4) had received their first treatment for psychological problems or had been given a psychiatric diagnosis more than 10 years earlier. The prevalence of moderate-to-severe depression was 115 (18%) in suicide-bereaved versus 28 (7%) in non-bereaved parents (RR 2.3; 95% CI 1.6 to 3.5). For those without psychological premorbidity, the relative risk was 2.3 (95% CI 1.4 to 3.6). 339 (51%) suicide-bereaved parents expressed worry over the child's psychological health during the month preceding the suicide and 259 (39%) had anticipated the suicide.
In parents who lost a child through suicide in Sweden we did not find a higher prevalence of long-term psychological premorbidity than among parents who had not lost a child; the more than twofold risk of depression among the bereaved can probably be explained by the suicide and the stressful time preceding the suicide.
PMCID: PMC3758979  PMID: 23996818
16.  The Phenomenology and Course of Depression in Parentally Bereaved and Non-Bereaved Youth 
To compare the phenomenology and course of bereavement-related depression to depression that occurred later in the course of bereavement and to depression in non-bereaved youth.
This sample is drawn from a cohort of parentally bereaved youth and non-bereaved controls followed for approximately 5 years. Three groups of depressed youth were compared with respect to symptoms, severity, duration, risk for recurrence, and correlates and risk factors: (1) a group with bereavement-related depression (BRD, n = 42), with the onset of a depressive episode within the first 2 months after parental loss; a group with later bereavement depression (LBD, n = 30), with onset at least 12 months after parental loss; and a non-bereaved control group with depression (CD, n = 30).
BRD episodes were similar to LBD and CD with respect to number of symptoms, severity, functional impairment, duration, risk for recurrence, and most risk factors and correlates. BRD, compared with both CD and LBD, were younger, exposed to fewer life events, and less likely to have experienced feelings of worthlessness. Also, caregivers of BRD showed higher rates of depression and post-traumatic stress disorder at the time of the depression compared with each of the other two groups.
BRD is similar to both LBD and CD in phenomenology, course, and risk factors, supporting a diagnostic and therapeutic approach to BRD similar to that for non–bereavement-related depressions. In the bereaved child who presents with depression shortly after parental death, the clinician should also be alert to caregiver depression and post-traumatic stress disorder.
PMCID: PMC3971905  PMID: 22525959
bereavement; depression; nosology
17.  Factors accounting for the association between anxiety and depression, and eczema: the Hordaland health study (HUSK) 
BMC Dermatology  2010;10:3.
The association between anxiety and depression, and eczema is well known in the literature, but factors underlying this association remain unclear. Low levels of omega-3 fatty acids and female gender have been found to be associated with both depression and eczema. Somatization and health anxiety are known to be associated with anxiety and depression, further, somatization symptoms and health anxiety have also been found in several dermatological conditions. Accordingly, omega-3 fatty acid supplement, female gender, somatization and health anxiety are possible contributing factors in the association between anxiety and depression, and eczema. The aim of the study is to examine the relevance of proposed contributing factors for the association between anxiety and depression, and eczema, including, omega-3 fatty acid supplement, female gender, health anxiety and somatization.
Anxiety and depression was measured in the general population (n = 15715) employing the Hospital Anxiety and Depression Scale (HADS). Information on eczema, female gender, omega-3 fatty acid supplement, health anxiety and somatization was obtained by self-report.
Somatization and health anxiety accounted for more than half of the association between anxiety/depression, and eczema, while the other factors examined were of minor relevance for the association of interest.
We found no support for female gender and omega-3 fatty acid supplement as contributing factors in the association between anxiety/depression, and eczema. Somatization and health anxiety accounted for about half of the association between anxiety/depression, and eczema, somatization contributed most. The association between anxiety/depression, and eczema was insignificant after adjustment for somatization and health anxiety. Biological mechanisms underlying the mediating effect of somatization are yet to be revealed.
PMCID: PMC2876073  PMID: 20412596
18.  Coexisting Anxiety and Depressive Symptoms in Patients with Heart Failure 
Among patients with heart failure (HF), anxiety symptoms may co-exist with depressive symptoms. However, the extent of overlap and risk factors for anxiety symptoms have not been thoroughly described.
To describe the coexistence of anxiety and depressive symptoms, and to determine the predictors of anxiety symptoms in patients with HF.
The sample consisted of 556 outpatients with HF (34% female, 62±12 years, 54% NYHA class III/IV) enrolled in a multicenter HF quality of life registry. Anxiety symptoms were assessed with the Brief Symptom Inventory-anxiety subscale. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI). We used a cut-point of 0.35 to categorize patients as having anxiety symptoms or no anxiety symptoms. Logistic regression was used to determine whether age, gender, minority status, educational level, functional status, comorbidities, depressive symptoms, and antidepressant use were predictors of anxiety symptoms.
One-third of patients had both depressive and anxiety symptoms. There was a dose-response relationship between depressive symptoms and anxiety symptoms; higher levels of depressive symptoms were associated with a higher level of anxiety symptoms. Younger age (OR= 0.97, p = .004, 95% CI 0.95–0.99) and depressive symptoms (OR = 1.25, p < .001, 95% CI 1.19–1.31) were independent predictors of anxiety symptoms.
Patients with HF and depressive symptoms are at high risk for experiencing anxiety symptoms. Clinicians should assess these patients for comorbid anxiety symptoms. Research is needed to test interventions for both depressive and anxiety symptoms.
PMCID: PMC3992982  PMID: 24408885
Cardiovascular; depressive disorder; anxiety disorder; heart failure
19.  Bereavement care interventions: a systematic review 
Despite abundant bereavement care options, consensus is lacking regarding optimal care for bereaved persons.
We conducted a systematic review, searching MEDLINE, PsychINFO, CINAHL, EBMR, and other databases using the terms (bereaved or bereavement) and (grief) combined with (intervention or support or counselling or therapy) and (controlled or trial or design). We also searched citations in published reports for additional pertinent studies. Eligible studies had to evaluate whether the treatment of bereaved individuals reduced bereavement-related symptoms. Data from the studies was abstracted independently by two reviewers.
74 eligible studies evaluated diverse treatments designed to ameliorate a variety of outcomes associated with bereavement. Among studies utilizing a structured therapeutic relationship, eight featured pharmacotherapy (4 included an untreated control group), 39 featured support groups or counselling (23 included a control group), and 25 studies featured cognitive-behavioural, psychodynamic, psychoanalytical, or interpersonal therapies (17 included a control group). Seven studies employed systems-oriented interventions (all had control groups). Other than efficacy for pharmacological treatment of bereavement-related depression, we could identify no consistent pattern of treatment benefit among the other forms of interventions.
Due to a paucity of reports on controlled clinical trails, no rigorous evidence-based recommendation regarding the treatment of bereaved persons is currently possible except for the pharmacologic treatment of depression. We postulate the following five factors as impeding scientific progress regarding bereavement care interventions: 1) excessive theoretical heterogeneity, 2) stultifying between-study variation, 3) inadequate reporting of intervention procedures, 4) few published replication studies, and 5) methodological flaws of study design.
PMCID: PMC503393  PMID: 15274744
Bereavement; intervention; systematic review
20.  Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11 
PLoS Medicine  2009;6(8):e1000121.
Holly Prigerson and colleagues tested the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and care of bereaved individuals at heightened risk of persistent distress and dysfunction.
Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction.
Methods and Findings
A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12–24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment.
The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11.
Please see later in the article for Editors' Summary
Editors' Summary
Virtually everyone loses someone they love during their lifetime. Grief is an unavoidable and normal reaction to this loss. After the death of a loved one, bereaved people may feel sadness, anger, guilt, anxiety, and despair. They may think constantly about the deceased person and about the events that led up to the person's death. They often have physical reactions to their loss—problems sleeping, for example—and they may become ill. Socially, they may find it difficult to return to work or to see friends and family. For most people, these painful emotions and thoughts gradually diminish, usually within 6 months or so of the death. But for a few people, the normal grief reaction lingers and becomes increasingly debilitating. Experts call this complicated grief or prolonged grief disorder (PGD). Characteristically, people with PGD have intrusive thoughts and images of the deceased person and a painful yearning for his or her presence. They may also deny their loss, feel desperately lonely and adrift, and want to die themselves.
Why Was This Study Done?
PGD is not currently recognized as a mental disorder although it meets the requirements for one given in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and in the World Health Organization's International Statistical Classification of Diseases and Related Health Problems, 10thEdition (ICD-10). Before PGD can be recognized as a mental disorder (and included in DSM-V and ICD-11), bereavement and mental-health experts need to agree on standardized criteria for PGD. Such criteria would be useful because they would allow researchers and clinicians to identify risk factors for PGD and to find ways to prevent PGD. They would also help to ensure that people with PGD get appropriate treatments such as psychotherapy to help them change their way of thinking about their loss and re-engage with the world. Recently, a panel of experts agreed on a consensus list of symptoms for PGD. In this study, the researchers undertake a field trial to develop and evaluate algorithms (sets of rules) for diagnosing PGD based on these symptoms.
What Did the Researchers Do and Find?
The researchers used “item response theory” (IRT) to derive the most informative PGD symptoms from structured interviews of nearly 300 people who had recently lost a close family member. These interviews contained questions about the consensus list of symptoms; each participant was interviewed two or three times during the two years after their spouse's death. The researchers then used “combinatoric” analysis to identify the most sensitive and specific algorithm for the diagnosis of PGD. This algorithm specifies that a bereaved person with PGD must experience yearning (physical or emotional suffering because of an unfulfilled desire for reunion with the deceased) and at least five of nine additional symptoms. These symptoms (which include emotional numbness, feeling that life is meaningless, and avoidance of the reality of the loss) must persist for at least 6 months after the bereavement and must be associated with functional impairment. Finally, the researchers show that individuals given a diagnosis of PGD 6–12 months after a death have a higher subsequent risk of mental health and functional impairment than people not diagnosed with PGD.
What Do These Findings Mean?
These findings validate a set of symptoms and a diagnostic algorithm for PGD. Because most of the study participants were elderly women who had lost their husband, further validation is needed to check that these symptoms and algorithm also apply to other types of bereaved people such as individuals who have lost a child. For now, though, these findings support the inclusion of PGD in DSM-V and ICD-11 as a recognized mental disorder. Furthermore, the availability of a standardized way to diagnose PGD will help clinicians identify the minority of people who fail to adjust successfully to the loss of a loved one. Hopefully, by identifying these people and helping them to avoid the onset of PGD (perhaps by providing psychotherapy soon after a death) and/or providing better treatment for PGD, it should now be possible to reduce the considerable personal and societal costs associated with prolonged grief.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Stephen Workman
The Dana Farber Cancer Institute has a page describing its Center for Psycho-oncology and Palliative Care Research
The UK Royal College of Psychiatrists has a leaflet on bereavement (in English, Welsh, Urdu, and Chinese)
The US National Cancer Institute also has information about coping with bereavement for patients and health professionals (in English and Spanish)
MedlinePlus has links to other information about bereavement (in English and Spanish)
The Journal of the American Medical Association has a patient page on abnormal grief
Harvard Medical School provides a short family health guide about complicated grief
Information on DSM-IV and ICD-10 is available
PMCID: PMC2711304  PMID: 19652695
21.  Primary care providers’ bereavement care practices: Recommendations for research directions 
Bereaved patients are often seen in primary care settings. While most do not require formal support, physicians may be called upon to provide support to some bereaved, particularly those with bereavement-related mental health disorders like complicated grief and bereavement-related depression. Research evidence on physician bereavement care is scant. We make recommendations for future research in this area.
Literature review, focusing on studies conducted between 1996 and 2013 in the United States. Searches of Medline and PsychInfo, along with hand searches of reference sections, was conducted.
The limited existing research indicates substantial gaps in the research literature, especially in the areas of primary care physician skill and capacity, patient-level outcomes, and the quality of research methodology. No U.S. studies have focused specifically on care for bereavement-related mental health disorders. We provide recommendations about how to improve research about primary care bereavement care.
The primary care sector offers ample opportunities for research on bereavement care. With greater research efforts, there may be improvements to quality of bereavement care in primary care, in general, and also to the accurate detection and appropriate referral for bereavement-related mental health conditions.
PMCID: PMC4418789  PMID: 24955568
bereavement; primary care; review; research recommendations; mental health; complicated grief; bereavement-related depression
22.  Neuroimaging for the Evaluation of Chronic Headaches 
Executive Summary
The objectives of this evidence based review are:
i) To determine the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) scans in the evaluation of persons with a chronic headache and a normal neurological examination.
ii) To determine the comparative effectiveness of CT and MRI scans for detecting significant intracranial abnormalities in persons with chronic headache and a normal neurological exam.
iii) To determine the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Clinical Need: Condition and Target Population
Headaches disorders are generally classified as either primary or secondary with further sub-classifications into specific headache types. Primary headaches are those not caused by a disease or medical condition and include i) tension-type headache, ii) migraine, iii) cluster headache and, iv) other primary headaches, such as hemicrania continua and new daily persistent headache. Secondary headaches include those headaches caused by an underlying medical condition. While primary headaches disorders are far more frequent than secondary headache disorders, there is an urge to carry out neuroimaging studies (CT and/or MRI scans) out of fear of missing uncommon secondary causes and often to relieve patient anxiety.
Tension type headaches are the most common primary headache disorder and migraines are the most common severe primary headache disorder. Cluster headaches are a type of trigeminal autonomic cephalalgia and are less common than migraines and tension type headaches. Chronic headaches are defined as headaches present for at least 3 months and lasting greater than or equal to 15 days per month. The International Classification of Headache Disorders states that for most secondary headaches the characteristics of the headache are poorly described in the literature and for those headache disorders where it is well described there are few diagnostically important features.
The global prevalence of headache in general in the adult population is estimated at 46%, for tension-type headache it is 42% and 11% for migraine headache. The estimated prevalence of cluster headaches is 0.1% or 1 in 1000 persons. The prevalence of chronic daily headache is estimated at 3%.
Computed Tomography
Computed tomography (CT) is a medical imaging technique used to aid diagnosis and to guide interventional and therapeutic procedures. It allows rapid acquisition of high-resolution three-dimensional images, providing radiologists and other physicians with cross-sectional views of a person’s anatomy. CT scanning poses risk of radiation exposure. The radiation exposure from a conventional CT scanner may emit effective doses of 2-4mSv for a typical head CT.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used to aid diagnosis but unlike CT it does not use ionizing radiation. Instead, it uses a strong magnetic field to image a person’s anatomy. Compared to CT, MRI can provide increased contrast between the soft tissues of the body. Because of the persistent magnetic field, extra care is required in the magnetic resonance environment to ensure that injury or harm does not come to any personnel while in the environment.
Research Questions
What is the effectiveness of CT and MRI scanning in the evaluation of persons with a chronic headache and a normal neurological examination?
What is the comparative effectiveness of CT and MRI scanning for detecting significant intracranial abnormality in persons with chronic headache and a normal neurological exam?
What is the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Research Methods
Literature Search
Search Strategy
A literature search was performed on February 18, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January, 2005 to February, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Systematic reviews, randomized controlled trials, observational studies
Outpatient adult population with chronic headache and normal neurological exam
Studies reporting likelihood ratio of clinical variables for a significant intracranial abnormality
English language studies
Exclusion Criteria
Studies which report outcomes for persons with seizures, focal symptoms, recent/new onset headache, change in presentation, thunderclap headache, and headache due to trauma
Persons with abnormal neurological examination
Case reports
Outcomes of Interest
Primary Outcome
Probability for intracranial abnormality
Secondary Outcome
Patient relief from anxiety
System service use
System costs
Detection rates for significant abnormalities in MRI and CT scans
Summary of Findings
One systematic review, 1 small RCT, and 1 observational study met the inclusion and exclusion criteria. The systematic review completed by Detsky, et al. reported the likelihood ratios of specific clinical variables to predict significant intracranial abnormalities. The RCT completed by Howard et al., evaluated whether neuroimaging persons with chronic headache increased or reduced patient anxiety. The prospective observational study by Sempere et al., provided evidence for the pre-test probability of intracranial abnormalities in persons with chronic headache as well as minimal data on the comparative effectiveness of CT and MRI to detect intracranial abnormalities.
Outcome 1: Pre-test Probability.
The pre-test probability is usually related to the prevalence of the disease and can be adjusted depending on the characteristics of the population. The study by Sempere et al. determined the pre-test probability (prevalence) of significant intracranial abnormalities in persons with chronic headaches defined as headache experienced for at least a 4 week duration with a normal neurological exam. There is a pre-test probability of 0.9% (95% CI 0.5, 1.4) in persons with chronic headache and normal neurological exam. The highest pre-test probability of 5 found in persons with cluster headaches. The second highest, that of 3.7, was reported in persons with indeterminate type headache. There was a 0.75% rate of incidental findings.
Likelihood ratios for detecting a significant abnormality
Clinical findings from the history and physical may be used as screening test to predict abnormalities on neuroimaging. The extent to which the clinical variable may be a good predictive variable can be captured by reporting its likelihood ratio. The likelihood ratio provides an estimate of how much a test result will change the odds of having a disease or condition. The positive likelihood ratio (LR+) tells you how much the odds of having the disease increases when a test is positive. The negative likelihood ratio (LR-) tells you how much the odds of having the disease decreases when the test is negative.
Detsky et al., determined the likelihood ratio for specific clinical variable from 11 studies. There were 4 clinical variables with both statistically significant positive and negative likelihood ratios. These included: abnormal neurological exam (LR+ 5.3, LR- 0.72), undefined headache (LR+ 3.8, LR- 0.66), headache aggravated by exertion or valsalva (LR+ 2.3, LR- 0.70), and headache with vomiting (LR+ 1.8, and LR- 0.47). There were two clinical variables with a statistically significant positive likelihood ratio and non significant negative likelihood ratio. These included: cluster-type headache (LR+ 11, LR- 0.95), and headache with aura (LR+ 12.9, LR- 0.52). Finally, there were 8 clinical variables with both statistically non significant positive and negative likelihood ratios. These included: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, and migraine type headache.
Outcome 2: Relief from Anxiety
Howard et al. completed an RCT of 150 persons to determine if neuroimaging for headaches was anxiolytic or anxiogenic. Persons were randomized to receiving either an MRI scan or no scan for investigation of their headache. The study population was stratified into those persons with a Hospital Anxiety and Depression scale (HADS) > 11 (the high anxiety and depression group) and those < 11 (the low anxiety and depression) so that there were 4 groups:
Group 1: High anxiety and depression, no scan group
Group 2: High anxiety and depression, scan group
Group 3: Low anxiety and depression, no scan group
Group 4: Low anxiety and depression, scan group
There was no evidence for any overall reduction in anxiety at 1 year as measured by a visual analogue scale of ‘level of worry’ when analysed by whether the person received a scan or not. Similarly, there was no interaction between anxiety and depression status and whether a scan was offered or not on patient anxiety. Anxiety did not decrease at 1 year to any statistically significant degree in the high anxiety and depression group (HADS positive) compared with the low anxiety and depression group (HADS negative).
There are serious methodological limitations in this study design which may have contributed to these negative results. First, when considering the comparison of ‘scan’ vs. ‘no scan’ groups, 12 people (16%) in the ‘no scan group’ actually received a scan within the follow up year. If indeed scanning does reduce anxiety then this contamination of the ‘no scan’ group may have reduced the effect between the groups results resulting in a non significant difference in anxiety scores between the ‘scanned’ and the ‘no scan’ group. Second, there was an inadequate sample size at 1 year follow up in each of the 4 groups which may have contributed to a Type II statistical error (missing a difference when one may exist) when comparing scan vs. no scan by anxiety and depression status. Therefore, based on the results and study limitations it is inconclusive as to whether scanning reduces anxiety.
Outcome 3: System Services
Howard et al., considered services used and system costs a secondary outcome. These were determined by examining primary care case notes at 1 year for consultation rates, symptoms, further investigations, and contact with secondary and tertiary care.
System Services
The authors report that the use of neurologist and psychiatrist services was significantly higher for those persons not offered as scan, regardless of their anxiety and depression status (P<0.001 for neurologist, and P=0.033 for psychiatrist)
Outcome 4: System Costs
System Costs
There was evidence of statistically significantly lower system costs if persons with high levels of anxiety and depression (Hospital Anxiety and Depression Scale score >11) were provided with a scan (P=0.03 including inpatient costs, and 0.047 excluding inpatient costs).
Comparative Effectiveness of CT and MRI Scans
One study reported the detection rate for significant intracranial abnormalities using CT and MRI. In a cohort of 1876 persons with a non acute headache defined as any type of headache that had begun at least 4 weeks before enrolment Sempere et al. reported that the detection rate was 19/1432 (1.3%) using CT and 4/444 (0.9%) using MRI. Of 119 normal CT scans 2 (1.7%) had significant intracranial abnormality on MRI. The 2 cases were a small meningioma, and an acoustic neurinoma.
The evidence presented can be summarized as follows:
Pre-test Probability
Based on the results by Sempere et al., there is a low pre-test probability for intracranial abnormalities in persons with chronic headaches and a normal neurological exam (defined as headaches experiences for a minimum of 4 weeks). The Grade quality of evidence supporting this outcome is very low.
Likelihood Ratios
Based on the systematic review by Detsky et al., there is a statistically significant positive and negative likelihood ratio for the following clinical variables: abnormal neurological exam, undefined headache, headache aggravated by exertion or valsalva, headache with vomiting. Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al. there is a statistically significant positive likelihood ratio but non statistically significant negative likelihood ratio for the following clinical variables: cluster headache and headache with aura. The Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al., there is a non significant positive and negative likelihood ratio for the following clinical variables: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, migraine type headache. The Grade quality of evidence supporting this outcome is very low.
Relief from Anxiety
Based on the RCT by Howard et al., it is inconclusive whether neuroimaging scans in persons with a chronic headache are anxiolytic. The Grade quality of evidence supporting this outcome is low.
System Services
Based on the RCT by Howard et al. scanning persons with chronic headache regardless of their anxiety and/or depression level reduces service use. The Grade quality of evidence is low.
System Costs
Based on the RCT by Howard et al., scanning persons with a score greater than 11 on the High Anxiety and Depression Scale reduces system costs. The Grade quality of evidence is moderate.
Comparative Effectiveness of CT and MRI Scans
There is sparse evidence to determine the relative effectiveness of CT compared with MRI scanning for the detection of intracranial abnormalities. The Grade quality of evidence supporting this is very low.
Economic Analysis
Ontario Perspective
Volumes for neuroimaging of the head i.e. CT and MRI scans, from the Ontario Health Insurance Plan (OHIP) data set were used to investigate trends in the province for Fiscal Years (FY) 2004-2009.
Assumptions were made in order to investigate neuroimaging of the head for the indication of headache. From the literature, 27% of all CT and 13% of all MRI scans for the head were assumed to include an indication of headache. From that same retrospective chart review and personal communication with the author 16% of CT scans and 4% of MRI scans for the head were for the sole indication of headache. From the Ministry of Health and Long-Term Care (MOHLTC) wait times data, 73% of all CT and 93% of all MRI scans in the province, irrespective of indication were outpatient procedures.
The expenditure for each FY reflects the volume for that year and since volumes have increased in the past 6 FYs, the expenditure has also increased with a pay-out reaching 3.0M and 2.8M for CT and MRI services of the head respectively for the indication of headache and a pay-out reaching 1.8M and 0.9M for CT and MRI services of the head respectively for the indication of headache only in FY 08/09.
Cost per Abnormal Finding
The yield of abnormal finding for a CT and MRI scan of the head for the indication of headache only is 2% and 5% respectively. Based on these yield a high-level estimate of the cost per abnormal finding with neuroimaging of the head for headache only can be calculated for each FY. In FY 08/09 there were 37,434 CT and 16,197 MRI scans of the head for headache only. These volumes would generate a yield of abnormal finding of 749 and 910 with a CT scan and MRI scan respectively. The expenditure for FY 08/09 was 1.8M and 0.9M for CT and MRI services respectively. Therefore the cost per abnormal finding would be $2,409 for CT and $957 for MRI. These cost per abnormal finding estimates were limited because they did not factor in comparators or the consequences associated with an abnormal reading or FNs. The estimates only consider the cost of the neuroimaging procedure and the yield of abnormal finding with the respective procedure.
PMCID: PMC3377587  PMID: 23074404
23.  Depressive Symptom Dimensions and Cardiovascular Prognosis among Women with Suspected Myocardial Ischemia: A Report from the NHLBI-Sponsored WISE Study 
Archives of general psychiatry  2009;66(5):499-507.
Symptoms of depression and cardiovascular disease overlap substantially. Differentiating between dimensions of depressive symptoms may improve our understanding of the relationship between depression and physical health.
To compare symptom dimensions of depression as predictors of cardiovascular-related death and events among women with suspected myocardial ischemia.
Cohort study of women with suspected myocardial ischemia who were evaluated at baseline for history of cardiovascular-related problems, depressive symptoms using the Beck Depression Inventory (BDI), and coronary artery disease severity via coronary angiogram. Principal components analyses (PCA) of the BDI items were conducted to examine differential cardiovascular prognosis according to symptom dimensions of depression.
The Women's Ischemia Syndrome Evaluation (WISE), a National Heart, Lung, and Blood Institute (NHLBI)–sponsored multi-center study assessing cardiovascular function using state-of-the-art techniques in women referred for coronary angiography to evaluate chest pain or suspected myocardial ischemia.
550 women (mean age = 58.4 [11.2] years) enrolled in WISE and followed for a median of 5.8 years.
Main Outcome Measures:
Cardiovascular-related mortality and events (stroke, myocardial infarction, and congestive heart failure).
Using a three-factor structure from PCA, somatic/affective (hazards ratio [HR]=1.35, 95% confidence interval [CI]=1.04-1.74) and appetitive (HR=1.42, 95%CI=1.21-1.68) but not cognitive/affective (HR=.89, 95%CI=.70-1.14) symptoms predicted cardiovascular prognosis in adjusted multivariate Cox regression analysis. Using a two-factor structure from PCA, adjusted results indicated that somatic (HR=1.63, 95% CI=1.28-2.08) but not cognitive/affective (HR=.87, 95% CI=.68-1.11) symptoms predicted worse prognosis.
In a sample of women with suspected myocardial ischemia, somatic but not cognitive/affective depressive symptoms were associated with an increased risk of cardiovascular-related mortality and events. These results support the need to research dimensions of depression in CVD populations and have implications for understanding the connection between depression and CVD.
Unstructured Abstract
Differentiating between dimensions of depressive symptoms may improve our understanding of the relationship between depression and cardiovascular disease (CVD). This study examined depressive symptom dimensions as predictors of cardiovascular-related death and events among women undergoing coronary angiography to evaluate suspected myocardial ischemia (n=550; mean age=58.4 [11.2] years). Baseline evaluation included depressive symptom assessment using the Beck Depression Inventory (BDI) and coronary artery disease severity testing via coronary angiogram. Incidence of the women's cardiovascular-related mortality and events (stroke, myocardial infarction, and congestive heart failure) was tracked for a median of 5.8 years. Principal components analyses (PCA) of the 21 BDI items were conducted to derive depression symptom dimensions. Using a three-factor structure, somatic/affective (HR=1.35, 95%CI=1.04-1.74) and appetitive (HR=1.42, 95%CI=1.21-1.68) but not cognitive/affective (HR=.89, 95%CI=.70-1.14) symptoms predicted cardiovascular prognosis in adjusted multivariate Cox regression analysis. Using a two-factor structure, adjusted results indicated that somatic (HR=1.63, 95% CI=1.28-2.08) but not cognitive/affective (HR=.87, 95% CI=.68-1.11) symptoms predicted prognosis. Thus, in a sample of women with suspected myocardial ischemia, somatic but not cognitive/affective depressive symptoms were associated with worse cardiovascular prognosis. These results support the need to research depressive symptom dimensions in CVD populations and have implications for understanding the connection between depression and CVD.
PMCID: PMC2697960  PMID: 19414709
24.  Distinguishing Bereavement from Depression in DSM-5: Evidence from Longitudinal Epidemiologic Surveys 
Psychiatric annals  2013;43(6):276-282.
Following the earlier versions of the diagnostic manual, the DSM-IV set a higher symptom and duration threshold for the diagnosis of major depression in individuals who have experienced recent bereavement—the bereavement exclusion criterion. This criterion excludes a diagnosis of major depression among those whose symptoms persist for less than two months, as long as they do not have marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. The DSM-5 committee, however, has proposed to remove this criterion from the upcoming DSM-5. The committee's decision was based on reviews of past literature. However, few past studies directly compared DSM-excluded bereavement-related depression to other major depressive disorder in representative population samples and had adequate power to detect differences. The results of these studies, therefore, did not provide strong evidence for the validity of bereavement exclusion. In this paper, we review three recently published analyses based on large epidemiologic samples that found significant differences between those with bereavement-excluded episodes and episodes meeting major depression criteria with regard to short-term risk of future depressive episodes, psychiatric comorbidity and other clinical and socio-demographic characteristics. In follow-ups ranging from 1 to 3 years, individuals with bereavement-excluded depressive episodes were significantly less likely to experience new episodes than those who met criteria for depression, and were not more likely to experience future episodes than those without any past history of depression. The findings from these new studies support the validity of the DSM-IV bereavement exclusion criterion and argue for preserving it in the new edition of the manual.
PMCID: PMC4517840
25.  Posttraumatic Stress and Complicated Grief in Family Members of Patients in the Intensive Care Unit 
Journal of General Internal Medicine  2008;23(11):1871-1876.
Family members of patients in intensive care units (ICUs) are at risk for mental health morbidity both during and after a patient’s ICU stay.
To determine prevalences of and factors associated with anxiety, depression, posttraumatic stress and complicated grief in family members of ICU patients.
Prospective, longitudinal cohort study.
Fifty family members of patients in ICUs at a large university hospital participated.
We used the Control Preferences Scale to determine participants’ role preferences for surrogate decision-making. We used the Hospital Anxiety and Depression Scale, Impact of Event Scale, and Inventory of Complicated Grief to measure anxiety and depression (at enrollment, 1 month, 6 months), posttraumatic stress (6 months), and complicated grief (6 months).
We interviewed all 50 participants at enrollment, 39 (78%) at 1 month, and 34 (68%) at 6 months. At the three time points, anxiety was present in 42% (95% CI, 29–56%), 21% (95% CI, 10–35%), and 15% (95% CI, 6–29%) of participants. Depression was present in 16% (95% CI, 8–28%), 8% (95% CI, 2–19%), and 6% (95% CI, 1–18%). At 6 months, 35% (95% CI, 21–52%) of participants had posttraumatic stress. Of the 38% who were bereaved, 46% (95% CI, 22–71%) had complicated grief. Posttraumatic stress was not more common in bereaved than nonbereaved participants, and neither posttraumatic stress nor complicated grief was associated with decision-making role preference or with anxiety or depression during the patient’s ICU stay.
Symptoms of anxiety and depression diminished over time, but both bereaved and nonbereaved participants had high rates of posttraumatic stress and complicated grief. Family members should be assessed for posttraumatic stress and complicated grief.
PMCID: PMC2585673  PMID: 18780129
critical care; primary care; psychology

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