Neuroendocrine mechanisms of grief and bereavement: A systematic review and implications for future interventions

Bereavement is associated with many negative behavioural, psychological and physiological consequences and leads to an increased risk of mortality and morbidity. However, studies specifically examining neuroendocrine mechanisms of grief and bereavement have yet to be reviewed. This systematic review is a synthesis of the latest evidence in this field and aims to draw conclusions about the implications of neurobiological findings on the development of new interventions. PRISMA guidelines for systematic reviews were used to search for articles assessing neuroendocrine correlates of grief. Findings were qualitatively summarised. The National Heart, Lung, and Blood Institute Study Assessment Tool was used to assess the quality of the included studies. Out of 460 papers, 20 met the inclusion criteria. However, most were of fair quality only. As a neuroendocrine marker, the majority of the studies reported cortisol as the outcome measure and found elevated mean cortisol levels, flattened diurnal cortisol slopes and higher morning cortisol in bereaved subjects. Cortisol alterations were moderated by individual differences such as emotional reaction to grief, depressive symptoms, grief severity, closeness to the deceased and age or gender. Research on neuroendocrine mechanisms of grief is still in its early stages regarding grief measures and the use and timing of neuroendocrine assessments. Most of the studies focus on cortisol as outcome, and only limited data exist on other biomarkers such as oxytocin. Future research might consider assessing a broader range of neuroendocrine markers and use longitudinal designs with a focus on the psychobiological reactions to loss. Based on this, individually tailored psychosocial interventions, possibly in the palliative care context, might be developed to prevent prolonged grief disorder.     

Maturation of the adrenocortical stress response: Neuroendocrine control mechanisms and the stress hyporesponsive period

During the first two weeks of life rat pups show a markedly reduced adrenocortical response to stress, and this period of adrenocortical quiescence has been termed the ‘stress non-responsive period’ (SNRP). The adaptive value of the SNRP can be understood in terms of the effects of glucocorticoids on CNS development: excessively high or low corticoid levels are associated with abnormal neural and behavioral development. We have attempted to explain adrenocortical activity during this period in terms of the unique pattern of glucocorticoid-receptor concentrations that exist in the brain and pituitary of the neonatal rat. This pattern of receptor concentrations results in a negative-feedback condition at the level of the brain and pituitary that ensures the low. stable corticoid levels that appear to be optimal for neuronal development in glucocorticoid-sensitive brain regions.     

Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence

Social vigilance is a behavioral strategy commonly used in adverse or changing social environments. In animals, a combination of avoidance and vigilance allows an individual to evade potentially dangerous confrontations while monitoring the social environment to identify favorable changes. However, prolonged use of this behavioral strategy in humans is associated with increased risk of anxiety disorders, a major burden for human health. Elucidating the mechanisms of social vigilance in animals could provide important clues for new treatment strategies for social anxiety. Importantly, during adolescence the prevalence of social anxiety increases significantly. We hypothesize that many of the actions typically characterized as anxiety behaviors begin to emerge during this time as strategies for navigating more complex social structures. Here, we consider how the social environment and the pubertal transition shape neural circuits that modulate social vigilance, focusing on the bed nucleus of the stria terminalis and prefrontal cortex. The emergence of gonadal hormone secretion during adolescence has important effects on the function and structure of these circuits, and may play a role in the emergence of a notable sex difference in anxiety rates across adolescence. However, the significance of these changes in the context of anxiety is still uncertain, as not enough studies are sufficiently powered to evaluate sex as a biological variable. We conclude that greater integration between human and animal models will aid the development of more effective strategies for treating social anxiety.     

The social determinants of mental health: implications for research and health promotion

Social determinants of health have come to greater prominence through the recent work of the WHO Commission on the Social Determinants of Health, and the Marmot Review of Health Inequalities in England. These reports also have significant implications for promotion of mental health in developed countries. In particular they reflect a growing research interest in the view that certain adverse social conditions may detrimentally affect mental or physical health by acting as chronic stressors. However, although the case for chronic arousal of stress systems as a risk factor for mental health is empirically well-founded, questions remain about how and why psychological exposure to certain kinds of proximal social conditions might contribute to such arousal. In this paper we argue that combining evidence and ideas from a number of disciplines, including public health research and psychiatry, presents an opportunity to understand the relationship better, and so inform complementary strategies in treatment, prevention and health promotion.     

Molecular and cellular mechanisms of cognitive function: implications for psychiatric disorders.

Recent studies on the molecular and cellular basis of learning and memory have brought us closer than ever to understanding the mechanisms of synaptic plasticity and their relevance to memory formation. Genetic approaches have played a central role in these new findings because the same mutant mice can be studied with molecular, cellular, circuit, and behavioral tools. Therefore, the results can be used to construct models that cut across levels of analytical complexity, forging connections from the biochemistry of the modified protein to the behavior of the mutant mice. These findings are not only improving our understanding of learning and memory, they are also enriching our understanding of cognitive disorders, such as neurofibromatosis type I. Mechanisms underlying long-term changes in synaptic function are likely to be at the heart of many cognitive and emotional processes in humans. Therefore, molecular and cellular insights into learning and memory undoubtedly will have a profound impact on the understanding and treatment of psychiatric disorders.     

Cognitive disabilities: measuring the social consequences of mental disorders

The disabilities associated with psychiatric illnesses can be separated into six cognitive levels that can be identified by functions the patient is able to perform, by the types of assistance required to compensate for dysfunctions, and by the social dysfunction observed in home and work environments. These cognitive levels can be used to measure the severity of mental disorders; changes in these levels reflect temporal changes in severity that are consequent to treatment and/or natural history of the condition. These cognitive levels can also be used to assess need for hospitalization and/or community placement, readiness for discharge from hospital, and effectiveness of treatment. A collaborative relationship between occupational therapists and psychiatrists is needed for the most effective use of these reliable and objective assessments of cognitive function levels in patients with psychiatric illness.     

Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorders

The endocannabinoid system is a widely distributed, neuromodulatory system which serves an integral role in regulating synaptic transmission. The presence of this system in stress-responsive neural circuits suggests that it may play a critical role in regulating neuroendocrine and behavioral responses to stress. Endocannabinoid content in limbic structures which regulate activation of the hypothalamic-pituitary-adrenal (HPA) axis is dynamically regulated by stress. Under conditions of acute stress, the endocannabinoid system tonically constrains activation of the HPA axis. During repeated exposure to aversive stimuli, the endocannabinoid system up-regulates in limbic structures, resulting in dampened neural activity in stress circuits, which could contribute to stress habituation. Disrupted endocannabinoid signaling, on the other hand, is associated with an inability to adapt to chronic stress. Therapeutically, these data suggest that the endocannabinoid system could be dysregulated in affective disorders, such as depression, which are characterized by maladaptive stress coping. In this review, we discuss the evidence demonstrating that the endocannabinoid system is affected by and can oppose the effects of prolonged stress and, as such, represents a potential target for the development of novel antidepressant agents.     

New implications for mental disorders treatment: pharmacogenetic studies of dopaminergic and serotonergic neurotransmission systems

The aim of this article is to summarize the present state of pharmacogenetical knowledge compiled and based on various publications in this matter. Thanks to developing cloning and DNA-analysis techniques it is possible to analyze numerous proteins synthetized in the central nervous system. Several polymorphism sites in coding genes have already been located--first of all for some genes coding receptors linked to protein G, especially for dopamine and serotonine receptors. Some of mutations may influence the primary structure of receptor protein and in that way be responsible for alteration of receptors functioning. This is likely to be the reason for the difference in reaction to drugs in many patients. A couple of trials dealing with patient's response to neuroleptics in correlation with receptor genes polymorphism have already been completed. The results are promising. The assumption that inventing new drugs should be correlated with collecting DNA samples from patients to evaluate further pharmacogenetical linkage seems to be essential.     

Desire for social interaction in children with autism spectrum disorders

In this experimental clinical study, a first attempt was made to examine the desire for social interaction in children with autism spectrum disorders (ASD). Children with ASD and typically developing (TD) children completed both an explicit measure (self-report) and an implicit measure (Face Turn Approach–Avoidance Task) of the desire for social interaction. On the explicit assessment, children with ASD clearly displayed lower scores reflecting less desire for social interaction than TD children. On the implicit assessment, children with ASD showed a stronger tendency to pull both social and non-social stimuli towards them, which indicates a general automatic tendency towards approach, as compared to the TD children. Possible reasons for this dissociation between the explicit and implicit desire for social interaction are discussed and directions for future research are provided.     

Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress

OBJECTIVE: Most research on the effects of severe psychological stress has focused on stress-related psychopathology. Here, the author develops psychobiological models of resilience to extreme stress. METHOD: An integrative model of resilience and vulnerability that encompasses the neurochemical response patterns to acute stress and the neural mechanisms mediating reward, fear conditioning and extinction, and social behavior is proposed. RESULTS: Eleven possible neurochemical, neuropeptide, and hormonal mediators of the psychobiological response to extreme stress were identified and related to resilience or vulnerability. The neural mechanisms of reward and motivation (hedonia, optimism, and learned helpfulness), fear responsiveness (effective behaviors despite fear), and adaptive social behavior (altruism, bonding, and teamwork) were found to be relevant to the character traits associated with resilience. CONCLUSIONS: The opportunity now exists to bring to bear the full power of advances in our understanding of the neurobiological basis of behavior to facilitate the discoveries needed to predict, prevent, and treat stress-related psychopathology.     

Community specialized social help services for patients with mental disorders: one year experience

This article describes one year's experiences of Foundation of Supporting Psychiatric Department Medical Academy of Warsaw in care of patients with mental disorders in two districts of Warsaw. The service was provided for open group of about 70-80 patients with the diagnosis of schizophrenia and depressive disorder recurrent. Introducing of this type of care resulted in reducing of the number of patient admitted to the hospital and in shortening of the mean hospitalization time. Moreover, last but not least, improved patient's life quality. The article contains also care reports illustrations successes and defeats in this type of care.     

Omissions in assessment of work roles: implications for evaluating social functioning and mental illness.

An analysis of data from a longitudinal study of individuals during and after psychiatric hospitalization found that multiple work roles often remain unconsidered in assessments of social functioning and psychiatric status. The inclusion of such multiple roles was found to be important for adequate measurement of productive functioning and to illuminate their interaction with individuals' psychopathology.     

The effects of prenatal social stress on behaviour: mechanisms and function

In this review, we summarise experimental animal studies on the effects of the social environment during pregnancy on the offsprings' behaviour, brain, and neuroendocrine function. We show that in non-human mammals the stability of the social environment in which the pregnant females live is critical for the offsprings' social and sexual behaviour later in life as well as for reproductive functioning, endocrine state and androgen and estrogen receptor distribution in specific parts of the brain. Based on these findings, we discuss different neuroendocrine mechanisms mediating the influence of the social environment during pregnancy on the offsprings' behaviour. We conclude that maternal steroids play a decisive role in shaping foetal brain development. However, a pituitary adrenocortical pathway need not always be involved. At least in some cases an involvement of the sympathetic adrenomedullary system seems to be possible. Concerning function, we favour the hypothesis that the behavioural effects of prenatal social stress are not necessarily the 'pathological' consequences of adverse social conditions (non-adaptive explanation). Contrarily, mothers could be adjusting their offspring to the environment in which they live during pregnancy in an efficient way (adaptive explanation).