Childhood maltreatment has been discussed as a risk factor for the development and maintenance of depression.
To examine the relationship between childhood maltreatment and adult depression with ...regard to depression incidence, severity, age at onset, course of illness and treatment response.
We conducted meta-analyses of original articles reporting an association between childhood maltreatment and depression outcomes in adult populations.
In total, 184 studies met inclusion criteria. Nearly half of patients with depression reported a history of childhood maltreatment. Maltreated individuals were 2.66 (95% CI 2.38-2.98) to 3.73 (95% CI 2.88-4.83) times more likely to develop depression in adulthood, had an earlier depression onset and were twice as likely to develop chronic or treatment-resistant depression. Depression severity was most prominently linked to childhood emotional maltreatment.
Childhood maltreatment, especially emotional abuse and neglect, represents a risk factor for severe, early-onset, treatment-resistant depression with a chronic course.
There is ample evidence showing that childhood maltreatment (CM) is a risk factor for the development of depression in adulthood. However, little is known about the psychological processes mediating ...this relationship. This study used a large community sample to investigate the mediating role of emotional, cognitive and/or interpersonal dysfunctions on the one hand and posttraumatic stress disorder symptoms on the other hand.
One thousand twenty seven participants of a community sample filled out an online survey. Mediation analyses were computed via linear structural equation modelling.
Results showed a significant mediation of the association between CM and adult depression via emotional impairments, depressogenic attribution style and symptoms of posttraumatic stress disorder. Our study design was cross-sectional and therefore did not allow testing temporal precedence of mediators and causality. Data was collected retrospectively, a confounding effect of current depressive symptoms on retrospective recall of CM therefore cannot be ruled out.
The a priori mediation model showed a good fit with the data. The model suggests promising objectives for further research on CM-related depression and potential treatment targets in the future.
We tested a VR lifeline exercise to alter spatio-temporal associations and intrusions of aversive autobiographical memories.
This was not superior to a non-personalized control group, but temporal ...associations and memory distancing predicted reduced re-experiencing.
Individuals with posttraumatic stress disorder (PTSD) often report intrusive memories that appear to lack the appropriate spatio-temporal context.
We examined whether focusing on the spatio-temporal context of aversive autobiographical memories reduces negative emotions, appraisals, and re-experiencing symptoms.
We recruited 109 healthy adults and had them rate emotionality, vividness, and re-experiencing of an aversive autobiographical memory. Furthermore, we assessed automatic associations of idiosyncratic memory triggers with the concepts 'past' vs. 'now', and self-reported sense of memory closure and distancing. To manipulate spatio-temporal memory (re-)organization, the experimental group (n = 53) performed a lifeline exercise in virtual reality (VR), where participants symbolically placed memory triggers along a path representing their own personal life story. The control group (n = 56) completed a non-personalized VR task.
We found a marked decrease in negative emotions, negative appraisals, and re-experiencing in the following week, but on average, the lifeline exercise was not superior to the control condition. However, those in the lifeline group with stronger trigger-past associations subsequently exhibited a more pronounced reduction in re-experiencing. Also, participants with a higher subjective sense of memory distancing reported less re-experiencing.
The findings lend tentative support for theoretical assumptions about PTSD, but the potential causal role of automatic associations with spatio-temporal information remains to be clarified.
The present study aimed to investigate the everyday emotional dynamics of depressed individuals, especially the role of emotional inertia, emotional context insensitivity, and emotional variability ...and instability. Using ecological momentary assessment, 40 currently depressed individuals and 40 healthy controls reported on their current emotional state and current activities 10 times a day for 4 consecutive days. There were no differences in the dynamics of positive affect (PA) between depressed and healthy subjects. Depressed participants' negative affect (NA), however, was found to be more inert than in healthy controls, while at the same time being more variable and more reactive to positive events. There was also an association between emotional instability and depression, but this was rendered nonsignificant when analyses were controlled for emotional variability. Altogether, emotional dynamics of NA appear to be more prominently disturbed in depression compared to PA. Results support earlier findings on NA emotional variability as well as inertia in depressed patients. In addition, there was some evidence for a mood brightening effect in depression.
The miR-15/107 family comprises a group of 10 paralogous microRNAs （miRNAs）,sharing a 5＇ AGCAGC sequence.These miRNAs have overlapping targets.In order to characterize the expression of miR-15/107 ...family miRNAs,we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members,and other selected miRNAs,in 11 human tissues obtained at autopsy including the cerebral cortex,frontal cortex,primary visual cortex,thalamus,heart,lung,liver,kidney,spleen,stomach and skeletal muscle.miR-103,miR-195 and miR-497 were expressed at similar levels across various tissues,whereas miR-107 is enriched in brain samples.We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations （enriched for cortical neurons,astrocytes and microglia,respectively）.In primary cultures of rat brain cells,several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system （CNS）.In addition to mature miRNAs,we also examined the expression of precursors （pri-miRNAs）.Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors.In summary,we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.
Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of ...dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared with controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy. These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease.
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•Dystrophic microglia are not increased in hippocampus of healthy human aging.•Dystrophic microglia are the most common morphology in neurodegenerative disease.•Dystrophic microglia had high FTL staining, suggesting altered iron homeostasis
Synapses may represent a key nidus for dementia including Alzheimer's disease (AD) pathogenesis. Here we review published studies and present new ideas related to the question of the specificity of ...synapse loss in AD. Currently, AD is defined by the regional presence of neuritic plaques and neurofibrillary tangles in the brain. The severity of involvement by those pathological hallmarks tends to correlate both with antemortem cognitive status, and also with synapse loss in multiple brain areas. Recent studies from large autopsy series have led to a new standard of excellence with regard to clinical–pathological correlation and to improved comprehension of the numerous brain diseases of the elderly. These studies have provided evidence that it is the rule rather than the exception for brains of aged individuals to demonstrate pathologies (often multiple) other than AD plaques and tangles. For many of these comorbid pathologies, the extent of synapse loss is imperfectly understood but could be substantial. These findings indicate that synapse loss is probably not a hallmark specific to AD but rather a change common to many diseases associated with dementia.
The largest segment of missing children in the United States includes runaways, children who run away from home, and thrownaways, children who are told to leave or stay away from home by a household ...adult. Although estimates vary, as many as 1 in 20 youth run away from home annually. These unaccompanied youth have unique health needs, including high rates of trauma, mental illness, substance use, pregnancy, and sexually transmitted infections. While away, youth who run away are at high risk for additional trauma, victimization, and violence. Runaway and thrownaway youth have high unmet health care needs and limited access to care. Several populations are at particular high risk for runaway episodes, including victims of abuse and neglect; lesbian, gay, bisexual, transgender, and questioning youth; and youth in protective custody. Pediatricians and other health care professionals have a critical role to play in supporting runaway youth, addressing their unique health needs, fostering positive relationships within their families and with other supportive adults, and connecting them with available community resources. This report provides clinical guidance for pediatricians and other health care professionals regarding (1) the identification of adolescents who are at risk for running away or being thrown away and (2) the management of the unique medical, mental health, and social needs of these youth. In partnership with national, state, and local resources, pediatricians can significantly reduce risk and improve long-term outcomes for runaway youth.
Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and ...gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available.
Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained ...by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.
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