| Acosta et al. (2018) |
N = 192 Gender: females (n = 96), males (n = 96) Age range: 19–38 Mage = 24.1 SD = 3.2 Type of loss: first-degree relative, spouse, or close friend; relationship or spousal breakup Time since loss: < 5 years |
Structural MRI Mini International Psychiatric Review Inclusion criteria: student status, age (18–40 years), right-handedness, no history of major psychiatric disorders |
Adult Attachment Style (RSQ) Affective loss (e.g., loss of a spouse, relative, friend, or relationship breakup; LTE-Q) |
Affective loss significantly associated with anxious attachment style (r = .18, p < .05) but not avoidant attachment style (r = −.10, p = .16) Anxious attachment positively associated with gray matter volume in the left insula and in the pars opercularis of left inferior frontal gyrus No association between affective loss and brain gray matter volume Sex-specific effects indicated affective loss in men was significantly associated with brain gray volume matter in left middle cingulate cortex |
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Arizmendi et al. (2016)*
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N = 28 (8 CG, 9 non-CG, 11 control) Control group: non-bereaved, married Gender: females (n = 23), males (n = 5) Age range: 62–82 Mage =71.9 SD = 4.6 Type of loss: not specified Time since loss: not specified |
fMRI: eCStroop task including 73-grief related words matched with neutral words. Eight alternating blocks of grief-related and neutral words. Participants rated words most relevant to their grief experience Inclusion Criteria: No presence of current major psychiatric disorder, no use of psychotropic medications since loss |
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CG group had slower reaction times and worse performance over the course of eCStroop blocks; control participants improved over the course of the task Non-CG group showed greater activity in grief compared to neutral trials in the right medial OFC (p = .001) and the rACC (p < .005) compared to controls. No differential rACC activity in the CG group compared to controls. CG and control groups showed significantly greater dACC activation in grief block 4 of the eCStroop compared to grief block 1 dACC activity did not differ significantly between CG and control groups |
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Arizmendi et al. (2018)*
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N = 37 (CG 17, non-CG 20) Gender: females (n = 28), males (n = 9) Age range: 55–80 Mage CG = 69.29, SD = 6.66; Mage non-CG = 68.36, SD = 6.44 Type of loss: spousal Time since loss: between 6 months and 3 years |
fMRI: AAT task with three stimulus categories (photos of spouse, stranger, and generic grief) INT OT/placebo manipulation (counterbalanced across two visits) Inclusion criteria: ages ranging from 25–80 years, not on psychotropic mediations, not enrolled in therapy/support groups targeted toward grief |
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INT OT condition showed an avoid bias for images of strangers (χ2 (1) = 4.35, p < .05) When viewing a spouse, CG/placebo group had increased activation in the right inferior frontal gyrus, precuneus, and right superior temporal sulcus (p < .001) compared to non-CG/INT OT group CG/INT OT group showed slower reaction times across all stimuli types compared to the placebo (F1,3299 = 42.21, p < .001) and non-CG/INT OT groups (F1,3781 = 69.27, p < .001) Non-CG/INT OT group showed increased activation in the superior temporal sulcus and right inferior frontal gyrus compared to CG/placebo group When ICG was included as a covariate, participants showed increased neural activity in the orbitofrontal (p <.001) and medial frontal/mid-cingulate regions when responding to generic grief compared to spouse stimuli No significant findings on NAcc activation |
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Bryant et al. (2020)*
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N = 117 (PGD 21, PTSD 45, MDD 26, Bereaved Control 25) Gender: females (n = 73), males (n = 44) Age range: Not specified MagePGD = 47.8, MagePTSD = 40.4, MageMDD = 31.5, MageControl = 45.1 SDPGD = 2.4, SDPTSD = 11.9, SDMDD =11.4, SDControl =14.2 Type of loss: Deceased partner (n = 4), parent (n = 8), child (n = 4), sibling (n = 5) Time since loss: Not specified |
fMRI: Passive face viewing task using standardized facial expressions of fear, anger, disgust, sadness, happiness, and neutral. Inclusion criteria: absence of neurological disorder, psychosis, or current substance dependence. No MDD or PTSD participants were bereaved. |
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Compared to bereaved control, PGD had greater activation in pregenual anterior cingulate cortex (z = 3.52, p = 0.005), left insula (cluster size = 872, z = 3.42, p = 0.042), right insula (z = 3.46, p = 0.036), left dorsolateral prefrontal cortex (z = 3.11, p = 0.028), right dorsolateral prefrontal cortex (z = 3.14, p = 0.026), right caudate (z = 3.26, p = 0.037), and pregenual anterior cingulate cortex-right palladium connectivity (z = 2.87, p = 0.037) during subliminal processing of happy faces Compared to PTSD and MDD, PGD had greater activation of medial orbitofrontal cortex (z = 3.18, p = 0.026) during supraliminal processing of sad faces Compared to MDD, PGD had greater activation in left amygdala (z = 3.21, p = 0.013), caudate (z = 3.43, p = 0.024), and left putamen (z = 3.57, p = 0.014) during subliminal processing of sad faces No difference between PGD, PTSD, and MDD during processing of happy faces. |
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Bui et al. (2019)*
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N = 139 (Bereaved with CG = 47; bereaved with MDD = 46; bereaved without any mental disorder = 46) Gender: females (n = 97), males (n = 42) Age range: 21–70 years Mage CG = 49.49, SD = 12.87; Mage MDD = 49.33, SD = 13.27; Mage bereaved controls = 48.65, SD = 12.70) Type of loss: death of a loved one Time since loss: ≥ 6 months |
Peripheral blood samples used to examine comparison of plasma OT levels Inclusion criteria: Loss of loved one within past 6 months Control groups: Matched on age and sex |
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Unadjusted regression analyses indicated that OT levels were significantly higher for CG group compared to MDD (p = .013), but no significant findings emerged when compared to bereaved control participants Adjusted regression models indicate that primary or probable CG diagnosis (ICG ≥ 30) was associated with significantly higher oxytocin levels (p = .001) |
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| Fernández-Alcántara et al. (2020) |
N = 38 (19 PGD, 19 nonbereaved) Control group: nonbereaved, sociodemographically matched with study group Gender: females (n=34, males (n = 38) Age range: 18–65 MagePGD= 40.42; MageControl=39.42 SDPGD=11.94; SDControl=12.42 Type of loss: any loved one Time since loss: ≤ 18 months (control group: ≥ 3 years if any loss) |
fMRI: Emotional Experience Task contrasting negative-, positive-, and death-valenced pictures (International Affective Picture System) Inclusion criteria (PGD group): loss of loved one within 18 months; ICG score > 25; no other psychiatric diagnoses |
PGD (ICG and ad-hoc clinical interview) Grief severity, past and present (TRIG) Depression and anxiety (SCL-90) PTSD: Global Assessment of PTSD (Spanish) Subjective emotional evaluation of pictures: Self-Assessment Manikin |
Amygdala and putamen activations in PGD group, but not in control group, correlated with TRIG-Present scores (r= −0.570, p= 0.013 vs. r= −0.490, p= 0.039, respectively); middle frontal gyrus activation in PGD group, but not control group, correlated with TRIG-Past (r= 0.522, p= 0.026 vs. r= 0.014, p= 0.955) While viewing negative-valenced pictures compared to fixation cross, PGD group had significantly greater activation of right inferior temporal cortex; control group had significantly greater activation in association and primary visual cortices Death vs. positive valence: PGD group had greater activation in amygdala, midbrain, PAG, cerebellum, and right hippocampus Negative vs. positive valence: PGD group had greater activation of midbrain, PAG, and right hippocampus No significant differences when comparing positive-valenced pictures to fixation cross, or death-valenced to negative-valenced pictures |
Amygdala Putamen Middle frontal gyrus Midbrain PAG Right hippocampus |
| Freed et al. (2009) |
N = 20 Gender: females (n = 16), males (n = 4) Age range: 22–62 Mage = 37.8 SD = 13.1 Type of loss: pet bereavement Time since loss: ≤ 3 months |
fMRI: Emotional Stroop task contrasting deceased-related with control words Inclusion criteria: loss of pet dog or cat within prior 3 months, no presence of psychiatric disorders |
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Attentional bias observed toward deceased-related words (p = .001). Participants made more errors during deceased word trials (p = .027). Bias magnitude associated with activity in right amygdala, insula, and DLPFC activity (ps < .01) Intrusiveness was associated with TRIG (r = .86, p < .000) and activation of ventral amygdala and rACC (p < .05) Amygdala activity was associated with induced sadness intensity (p < .05) Avoidance was associated with deactivation of the dorsal amygdala and DLPFC (ps < .05) High DLPFC-amygdala functional connectivity associated with reduced attentional bias (r = −.50), while low rACC-amygdala functional connectivity predicted sadness intensity (r = −.70) |
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| Gundel et al. (2003) |
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fMRI: 15 picture-word composites (grief versus neutral related words/photo of loved one versus a strange) Skin conductance Grief intensity Inclusion criteria: female gender, right-handedness, absence of psychiatric disorders |
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Three brain regions were activated by the picture and word factors: posterior cingulate cortex, medial/superior frontal gyrus, and cerebellum In the picture factor, the cuneus, superior lingual gyrus, insula, dACC, inferior temporal gyrus, and fusiform gyrus were activated (ps <.001, uncorrected) In the word factor, the precuneus, precentral gyrus, midbrain, and vermis were activated (ps <.001, uncorrected) |
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| Huang et al. (2018) |
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8-week MBCT fMRI: Numerical Stroop task (pre- and post-intervention) Inclusion criteria: native Mandarin speakers, no previous experience with mindfulness meditation, no presence of psychiatric disorders |
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Intervention reduced activation of the dorsal attentional network, including the middle frontal gyrus and superior parietal gyrus Improvements on reaction time in incongruent trials (F1,18 = 6.73, p < 0.018) Activation of the posterior cingulate cortex (r = .34, p < .04) and thalamus were associated with TRIG (r = .33, p < .05). Anxiety associated with activity in the posterior cingulate cortex (r = .36, p < .03). Lower grief and anxiety associated with reduced brain activations of posterior cingulate cortex or thalamus involved in the Stroop test |
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| Jain et al. (2019) |
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fMRI: involved 2×2 factorial design of picture-word composites of the caregivers’ loved one or a stranger (matched for age, sex, and race) together with a grief-related or neutral word, dementia family caregivers enrolled in either 4 weeks of PMR or MIT Inclusion criteria: must be primary source of assistance or support for the care recipient, with a score of > 9 on PHQ |
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Significant negative association was found between grief and mindfulness (r = −0.70, 95% CI −0.87 to −0.41, p ≤ .01) Picture-factor evoked two clusters of activation: left posterior cingulate/precuneus regions and bilateral anterior cingulate gyri (p ≤ .025) Word-factor evoked three clusters of activation: anterior cingulate cortex, posterior cingulate, and supramarginal gyrus (p ≤ .025) Improvement in grief was associated with increased brain activation in the precuneus (t = −4.78, d = −3.6) and anterior cingulate (t = −5.65, d = −4.3) |
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| McConnell et al. (2018) |
N = 25 (9 CG, 7 non-CG, 9 control) Control group: non-bereaved, married Age range: not specified Gender: females (n = 21), males (n = 4) Mage = 71.4 SD = not specified Type of Loss: spousal Time since Loss: x = 21.19 months |
fMRI: involved photos presented in an event-related design for 60 trials with 5 photos of participants’ spouses and 5 photos of a stranger (matched for age, sex, race, and background), manipulation check post-scan Inclusion criteria: older adults, death of a spouse in the last 3 years, or non-bereaved married controls w/o any loss of first-degree relative in the past 3 years |
Depression (BDI) Grief (ICG) |
No significant difference in activity between the three groups for spouse vs. stranger or anticipation vs. photo Higher self-reported yearning predicted activation in the subgenual anterior cingulate during the anticipation period compared to viewing photo of spouse (z = 3.11, p < .005, cluster size = 25) BDI showed no significant association with activation of sACC when included as regressor |
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| Najib et al. (2004) |
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BOLD fMRI: involved females who experienced upsetting romantic loss rating affect sfter viewing self-reported sad ruminative thought about ex-lover and neutral thought about an acquaintance Inclusion criteria: right-handed, premenopausal females, who had experienced a break-up/separation of relationship lasting ≥ 6 months, with absence of psychiatric disorder, psychotropic medication, pregnancy/lactation, and/or MRI contraindications |
Anxiety (Hamilton Anxiety Rating Scale) Cloninger’s Temperament and Character Inventory Depression (BDI, Hamilton Depression Rating Scale) Positive and Negative Affect Schedule Psychiatric History (SCID) Romantic loss/Grief (modified ICG) |
Significant increase in activation in cerebellum, posterior pons, posterior temporal cortex, posterior cingulate, parietal cortex, and occipital cortex during ruminative thought (p < .01) Significant decrease in activation in the subcortex, medial and lateral temporal cortices, insula, anterior cingulate, and frontal cortex during ruminative thought (p < .01) Negative association between brain activity in regions of interest for ruminative thought and subject’s baseline grief inventory score (r = 0.93, df = 7, p = 0.0003; z = 3.48) |
Cerebellum Cingulate Cortex (anterior) Frontal Cortex Occipital Cortex Parietal Cortex Pons Temporal Cortex (posterior, medial, lateral) |
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O’Connor et al. (2018)*⌘
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Idiographic Approach Avoidance Task response to images of deceased spouse, a living loved one, and a stranger (matched for age and sex) following placebo or OT in spousally bereaved older adults Inclusion criteria: not specified |
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Analysis revealed a main effect of CG Those with CG responded more slowly in the OT condition (p < .01), suggesting that neuropeptide oxytocin play a role in motivation systems of individuals with CG |
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O’Connor et al. (2015)*⌘
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N = 26 (8 CG, 9 non-CG, 9 controls) Age range: not specified Gender: not specified Mage = not specified SD = not specified Type of Loss: spousal Time since Loss: not specified |
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Bilateral hemodynamic responses in the amygdala and right orbitofrontal cortex were significantly activated (z = 3.93, p < .005) in CG group compared to Non-CG group CG group showed activation in precuneus and mid-cingulate regions in comparison to Non-CG and control groups |
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| O’Connor et al. (2007) |
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ECG and BOLD fMRI: involved 2×2 factorial design of picture-word composites of the caregivers’ loved one or a stranger together with a grief-related or neutral word Inclusion Criteria: right-handed females, who had experienced the loss of first-degree relative in the past year, with absence of Axis I psychiatric and medical disorders |
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Participants with higher tonic RSA had lower subjective reports of grief during scanning (in a comparison of the grief and neutral conditions) (RSA (6.16 ± 1.11), subjective rating of grief (5.9 ± 2.06); r = −0.74, p < 0.05) The PCC medial and superior frontal gyrus, and cerebellum were all co-activated by grief words and photos of the bereaved A significant positive association was found with the right cuneus (p = 0.009) and a negative association was found with the right PCC (p = 0.045) with the activation of Deceased>Stranger contrast A significant positive association was found with the left cuneus (p = 0.001) and PHG (p = 0.043) with the activation of Grief Word>Neutral Word contrast A significant positive association was found between sACC/orbitofrontal cortex and posterior cingulate activity in the Deceased>Stranger contrast (p < 0.001) |
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| O’Connor et al. (2009) |
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Saliva collection and fMRI task: involved 2×2 factorial design of picture-word composites of the caregivers’ loved one or a stranger (matched for age, sex, and race, environment) together with a grief-related or neutral word Inclusion criteria: females who had experienced loss of their sister or mother in the past 5 years, with absence of mood disorders, smoking and diseases of the immune system |
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Inflammatory markers (IL-1β and sTNFrII) were positively associated with ventral prefrontal activation (sACC and OFC) as well as other regions important in the emotional task such as noun retrieval (temporal cortex), and visual processing (cuneus and fusiform gyrus) (p < .0001) A significant positive association was found between sACC and freely recalled grief-related words (r = 0.50, p < 0.04), and the association between sACC and freely recalled neutral words (r = 0.27, p < 0.29) No significant associations found in multiple regression analysis. |
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| O’Connor et al. (2013) |
N = 16 Age range: not specified Gender: females (n = 14), males (n = 2) Mage = 64 SD = 4.3 Type of Loss: any (44% parent, 31% spouse, 6% child, 13% sibling, and other) Time since Loss: x = 87 months |
Blood sample collection as part of am ongoing randomized trial of Interpersonal Therapy versus Complicated Grief Therapy Inclusion criteria: score of ≥ 30 on the ICG, participants were asked to abstain from food, caffeine, and smoking ≥ 4 hours prior to blood draw |
Depression (BDI-II) Grief (ICG) |
Paired-sample t-test revealed the ICG was significant (t = 7.44, p < .001). The mean level ICG score at pre-treatment was 44.6 (SD = 11.5) and 23.5 (SD = 11.0) at post-treatment Epinephrine at pretreatment predicted the post-treatment ICG score, accounting for the pre-treatment ICG score (F (16, 2) = 6.68, p = 0.01, βlogE = 0.53, βICG = 0.48) Norepinephrine and dopamine levels at pre-treatment were not significant predictors of post-treatment ICG scores |
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O’Connor et al. (2008)*
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N = 23 (11 CG, 12 Non-CG) Age range: not specified Gender: females (n = 23) Mage = 43.7 SD = 10 Type of Loss: mother or sister Time since Loss: < 5 years |
Event-related fMRI task: involved 2×2 factorial design of picture-word composites of the caregivers’ loved one or a stranger (matched for age, sex, and race, environment) together with a grief-related or neutral word Inclusion criteria: females who had experienced loss of their sister or mother within 5 years, absence of Axis I disorders |
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Greater reward-related activity occurred in the CG group relative to the Non-CG group The NAcc was more active after presented grief-related words than neutral words in CG group compared to Non-CG group (t = 3.51, p < 0.001, 15 voxels) A significant positive correlation was found between NAcc activation and self-reported yearning for the deceased in the grief word comparison (r = .42, p < .05) Both CG (p ≤ .05) and non-CG (p < .01) groups showed significant activity in (pain-related regions) dACC, insula, and PAG in the comparisons of the deceased vs. stranger pictures and grief vs. neutral words The left insula was found to be more active in the Non-CG group during the viewing of grief-related vs. neutral words (t = 4.20, p < 0.001, 87 voxels) |
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Saavedra Perez et al. (2015)*
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N = 5501 Control group: individuals who were mourning over someone with severe disease/pet Age range: > 45 years old Gender: females (n = 2529), males (n = 2927) Mage control = 60.7, Mage non-CG = 62.4, Mage CG= 61.9 SD
control = 8.6, SD
non-CG = 9.3, SD
CG = 8.1 Type of loss: not specified Time since Loss: not specified |
fMRI: The study assessed differences in cognitive functions & brain volume in individuals with either no, normal, or complicated grief. Population-Based Inclusion criteria: MMSE score > 23, no major depression, ICG score < 22, no missing data, no dementia |
Attention, Concentration, Executive Function (Stroop Test) Cognitive Functions (MMSE) Grief (ICG) Processing Speed (LDST) Word Fluency Task |
Complicated grief group performed worse in domains of executive function, & information processing speed, & had a lower total brain volume as measured by structural brain imaging. No significant differences found in cognition & structural brain changes between persons with normal grief & the controls |
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| Schiele et al. (2018) |
N = 96 Age range: not specified Mage = 40.01 SD = 12.74 Gender: females (n = 68), males (n = 25) Type of loss: significant person Time since Loss: not specified |
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OXTR genotype interacted with BI &, on a trend-level, with adult SA, to increase CG Higher levels on the RSRI & ASA-27 scales, respectively, were related to higher ICG scores in GG genotype carriers Gender & age had no significant associations No significant associations were observed between OXTR & RSRI or ASA-27 |
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| Schneck et al. (2017) |
N = 23 Age range:18–65 Gender: females (n = 19), males (n = 4) Mage = 46 SD = 13.6 Type of loss: 1st degree relative, spouse, or partner Time since Loss: 3–14 months |
Measure Development: A machine learning approach was applied to fMRI (neural decoding) to develop a measure of ongoing deceased-related processing Population-Based Inclusion criteria: medically healthy, bereaved of a loved one 3–14 months ago |
Avoidance of Reminders of Loss (IES) Deceased, Living, Self-Related Thought (SART) Grief (ICG) Mental representations of the deceased (fMRI) |
Reliability was acceptable for both the ICG scale (∝ = .96) & IES avoidance subscale (∝ = .76) ICG score associated with avoidance, arousal during the mental representations of deceased task, frequency of thinking about the deceased on the SART, & average motion during the SART |
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| Schneck et al. (2019) |
N = 29 Age range:18–65 Gender: females (n = 23), males (n = 6) Mage = 44.06 SD =13.65 Type of loss: 1st degree relative or partner Time since Loss: 3–14 months |
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Avoidant grievers monitor the contents of their mind wandering Monitoring was linked to a reduced likeliness that mental representations of the deceased, arising during mind wandering, would lead to a conscious thought of loss Avoidant grievers still displayed more intrusive thoughts of loss overall on the task |
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| Schneck et al. (2019) |
N = 29 Age range:18–65 Gender: females (n = 23), males (n = 6) Mage = 44 SD =13 Type of loss: 1st degree relative or partner Time since Loss: 3–14 months |
Measured ongoing fluctuations in a neural proxy of d-SA during a neutral task to identify self-generated unconscious loss processing Population-Based Inclusion criteria: bereaved by a loved one 3–14 months ago & medically healthy |
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Engagement of d-SA during a neutral task, in the absence of a conscious thought of the deceased, associated with less severe grieving (r25 = −.711, p < .001, 95% CI = −0.89 to −0.42) Concurrent neural activity in temporal parietal junction & dorosolateral prefrontal cortex indicated combination of social processing & conscious control |
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| Schneck et al. (2018) |
N = 25 Age range: 18–65 Gender: females (n = 23), males (n = 2) Mage = 45 SD = 13 Type of loss: 1st degree relative or partner Time since Loss: 3–14 months |
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Attachment Style (AAS) Complicated Grief (ICG) Depression (BDI) Emotional Pain (TRIG) Emotional Selective Attention (Emotional Stroop Task) General Selective Attention (Standard Stroop Task) Intrusive Thinking (IES-R) Neural circuitry (fMRI) |
Slower RT to deceased-related versus living-related words demonstrates attentional bias to deceased (B= 0.012, t2831 = 2.73, p < .006, 95% confidence interval [CI], 0.003, Cohen’s d = 0.85), which was associated with greater intrusive thinking & general CG severity, but not emotional components of grief such as sadness, pain, & yearning Results remained significant when controlling for the effect of time since loss, CG severity, age, BDI score, number of prior major depressive episodes, suicide loss, & medication use on RT |
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