Stress is associated with poor mental health, specifically anxiety and depression, and stress and mental health problems are predictors of substance dependence and relapse. Social characteristics, such as racial/ethnic minority status, female gender, and low socioeconomic status, are often associated with increased psychological distress and substance use disorders. Pearlin’s social stress theory postulates that this association is due to increased exposure to stress and subsequent experiences of distress related to social disadvantage and decreased access to resources for coping with stress. This project uses a social stress theoretical perspective to examine predictors of substance use after treatment entry and follow-up addiction severity in a large sample of Kentucky substance abuse treatment participants (N = 1123). A conceptual model is tested to determine if social characteristics along with psychological distress, perceived stress, and economic hardship are predictors of substance use and follow-up addiction severity. In addition, since recovery support, efficacy, and self-control have been previously identified as mediators in the stress and relapse processes these factors were included as mediators in the model tested. The conceptual model was tested with three outcome variables, substance use between baseline and 12-month follow-up, follow-up alcohol addiction severity, and follow-up drug addiction severity. Bivariate and multivariate analyses, including logistic regression and ordinary least squares regression, were used to test conceptual models with the full sample and also with a subsample with baseline substance use indicative of potential substance dependence. Findings indicated that significance of predictors varied depending on outcome variable, although recovery support, efficacy, and self-control were significant predictors of all three dependent variables. Findings for each outcome variable are discussed, as well as limitations of the present study, implications for social work practice, and implications for future research.

Loving-kindness meditation (LKM) has the potential to improve intrapersonal and interpersonal functioning. This unique quality of LKM makes it a desirable candidate for buffering the stress of being social evaluated or socially excluded. Using the Trier Social Stress Test and the Cyberball social exclusion paradigm, the present study investigated the effectiveness of a brief LKM session in buffering against social evaluative and social exclusion stress. Three specific questions were addressed: In what domains can LKM exert positive effects? For whom does it work? And, how does it work? One hundred and thirteen participants (N = 113, 49 men) were randomly assigned to either a 10-minute LKM session or a 10-minute visualization control session. Findings showed that even just 10 minutes of LKM had an immediate relaxing effect as evidenced by increased respiratory sinus arrhythmia (RSA), an index of parasympathetic cardiac control, and decreased respiration rate. In addition, the brief LKM intervention led to greater implicit positivity towards the self relative to the control intervention (p = .052). The brief LKM intervention also protected against some of the negative physiological and psychological effects of social stress. The majority of these effects are moderated by trait social anxiety and pre-meditation mood states (or pre-meditation mood state alone). Contrary to expectation, trait social anxiety alone did not moderate any of the LKM effects. Importantly, receiving a brief session of LKM while not being in a positive mood or being in a negative mood led to iatrogenic physiological and psychological effects. Providing an explanation for one of LKM's effects, findings showed that change in RSA during LKM fully mediated the LKM Intervention x Positive Affect interaction effect on change in post-social-stress RSA. In conclusion, findings of the present study have extended our understanding of LKM and have specific implications for future research and practice.

To determine major areas of stress for adolescents, ninety-six sixteen and seventeen year olds were given a questionnaire which listed thirty-two situations which the subjects ranked in degrees of stress. The hypotheses examined the degree of family related and social related stress, the relationship of stress to age and sex, and the correlation between grade average and degree of stress. The first three hypotheses were tested by the t-test for mean differences. The fourth hypothesis used a Spearman rank order correlation coefficient. There was a difference in social stress and family stress, but no significant difference in stress of males and females or sixteen and seventeen year olds, and no significant correlation between grades and stress.

A majority of Americans regularly consume alcohol, but the risk factors leading to excessive drinking and alcohol abuse are unevenly distributed throughout the population. Genetic differences can account for only 40-60% of this variability. While variations in ethanol preference drinking in rodent models have been reported, the neurobiological factors underlying these behaviors are still not completely understood. Thus, these studies were designed to determine behavioral and molecular factors associated with the initiation of ethanol drinking preference in an inbred mouse model. We harnessed the power of inter-individual variation of ethanol drinking within an inbred mouse strain to essentially eliminate genetic variability and focus on environmental factors. Our studies have characterized robust, persistent individual variability in ethanol intake in C57 mice using a two-bottle choice paradigm. Ethanol intake differences were not due to litter effects or differences in taste preference. Social rank nor basal anxiety phenotypes could account for ethanol preference. Based on the shared co-morbidity of anxiety and alcoholism, and that alcoholics report anxiety and stress reduction as major motivational factors for drinking, we used an ethologically-relevant social defeat model to investigate stress-influences on ethanol drinking. We found that social defeat has bidirectional effects on ethanol drinking. Mice with a low predilection for ethanol tend to increase drinking following social stress while high preference mice decrease drinking. Even though social defeat produced a measurable physiological response in mice, defeat stress did not alter anxiety measures in the light-dark box. Thus, the current findings did not fully support the tension-reduction hypothesis of alcoholism. In order to determine the molecular factors underlying these differences in ethanol preference drinking, we employed genome-wide expression profiling to identify gene networks altered in ethanol-preferring and ethanol-avoiding mice. Genes involved in synaptic vesicle release, glutamate and BDNF signaling were differentially altered in drinking mice. Following stress-influenced ethanol drinking, expression profiling identified transcripts involved in dopamine signaling, the extra-hypothalamic stress response and alterations in steroid and glucocorticoid synthesis. Most importantly, these expression studies and behavioral analysis following histone deacetylase inhibition may be the first to implicate epigenetic factors involving chromatin acetylation and/or methylation as contributing to environmental modulation of ethanol intake.

A depressão na adolescência pode ser ocasionada devido à presença de estresses sociais, como o bullying, mas não se sabe por que apenas alguns indivíduos apresentam a depressão. Mudanças na neurotransmissão serotoninérgica relacionam-se a distúrbios comportamentais, sendo que alterações na expressão do receptor 5-HT6 poderiam desempenhar funções na cognição, memória e alterações do humor. O objetivo deste trabalho foi verificar a participação de alterações na expressão cerebral do receptor 5-HT6 na resiliência e suscetibilidade aos efeitos negativos do estresse psicossocial em camundongos machos e adolescentes. Nossos dados comportamentais demonstraram anedonia e esquiva social em apenas uma parcela dos animais subjugados socialmente (~50-60%). A expressão proteica do receptor 5-HT6 não diferiu em nenhuma das áreas cerebrais analisadas. A expressão gênica apresentou redução em ambos os subgrupos, no estriado e apenas nos suscetíveis, no hipotálamo. A localização cerebral do receptor 5-HT6 ocorreu no núcleo paraventricular do hipotálamo e no tubérculo olfatório. / Depression in adolescence may be caused due to social stresses, like bullying, but the reasons in which just a part of these individuals are affected by depression are unknown. Changes in serotoninergic neurotransmission are related with several behavioral disorders, and changes in the 5-HT6 receptor could have an important role on cognition, memory and mood disorders. The aim of this work was verify the participation of brain expression changes of 5-HT6 serotoninergic receptor in the resilience and susceptibility under the negative effects of the psychosocial stress in adolescent male mice. Our behavioral data showed anhedonia and social avoidance in one part of the subjugated animals (~50-60%). The protein expression of the 5-HT6 receptor did not differ in any brain areas that was studied. The gene expression showed a decrease in both subgroups, in the striatum, and a decrease only in the susceptible subgroup, in the hypothalamus. The brain localization of 5-HT6 receptor was in the hypothalamus paraventricular nucleus and in the olfactory bulb.

O cérebro não atinge sua completa maturidade até a idade adulta, tornando os adolescentes especialmente vulneráveis aos efeitos do estresse. Nesta etapa da vida, o bullying é um fator de risco que pode levar ao desenvolvimento da depressão, no entanto, não está claro porque alguns indivíduos são mais suscetíveis que outros. O óxido nítrico (NO), uma importante molécula sinalizadora no organismo, é sintetizada principalmente pela enzima óxido nítrico sintase neuronal (nNOS) no sistema nervoso central. Estudos sugerem que o NO e a nNOS poderiam desempenhar um importante papel na fisiopatologia da depressão, no entanto, ainda não foram realizadas pesquisas sobre a participação da nNOS no fenômeno da resiliência e suscetibilidade à depressão no período da adolescência. Por tanto, o objetivo deste trabalho foi estudar os efeitos da subjugação social prolongada em camundongos machos adolescentes C57BL/6 resilientes e suscetíveis a este tipo de estresse sobre comportamentos emocionais, bem como sobre a expressão gênica, proteica e a atividade enzimática da nNOS em algumas regiões cerebrais. Nossos resultados mostraram que alguns animais expostos ao estresse social prolongado desenvolveram esquiva social (56,7%) no teste de interação social e anedonia (50%) no teste de preferência por sacarose. Estes animais foram denominados suscetíveis. No entanto, outra parcela de animais não mostraram estas alterações comportamentais e foram denominados resilientes. Nossas análises moleculares mostraram que somente os camundongos resilientes apresentaram uma diminuição na expressão proteica e gênica da nNOS no hipocampo (HC) e no córtex pré-frontal (CPF), áreas comumente relacionadas com a depressão. Os camundongos suscetíveis apresentaram valores semelhantes aos controle nessas áreas cerebrais. Curiosamente, o estriado dorsal (ED), área utilizada como controle negativo, apresentou alterações na expressão gênica, proteica e na atividade enzimática nos animais resilientes e suscetíveis. Adicionalmente, foram analisadas as concentrações séricas dos nitratos e nitritos sistêmicos (NOx). Os camundongos resilientes apresentaram maiores concentrações destes metabolitos quando comparado com os animais suscetíveis. Em conclusão, nossos dados mostram que o estresse social prolongado é capaz de induzir comportamentos anedônicos e de esquiva social em camundongos machos adolescentes. As análises moleculares indicam que a resiliência a este tipo de estresse está associada à diminuição gênica e proteica da nNOS no HC e no CPF e ao aumento dos níveis séricos dos NOx. Além disso, as alterações moleculares no ED estariam sugerindo um papel para essa área na resposta do organismo frente ao estresse social. / The brain does not reach full maturity until adulthood, making adolescents especially vulnerable to the effects of stress. At this period of life, bullying is a risk factor for developing depression; however, it is unclear why some individuals are more susceptible than others. Nitric oxide (NO), an important neurotransmitter in the organism, is mainly synthetized by the neuronal NO synthase (nNOS) in the central nervous system. Several studies suggest that NO and nNOS can play an important role in the pathophysiology of depression, nevertheless, no research has been done yet on the participation of nNOS in the phenomenon of resilience and susceptibility to depression during adolescence. Therefore, the objective of this work was to study the effects of prolonged social defeat in adolescent male mice C57BL/6 resilient and susceptible to this type of stress on emotional behaviors, as well as on the gene expression, protein and enzymatic activity of nNOS in some brain regions. Our results showed that some animals exposed to prolonged social stress developed social approach-avoidance (56.7%) in social interaction test and anhedonia (50%) in sucrose preference test. These animals were called susceptible. However, remaining animals did not show these behavioral alterations and they were classified as resilient. Our molecular tests showed that resilient animals had a reduction nNOS gene and protein expression in hippocampus (HC) and prefrontal cortex (PFC), areas commonly related with depression. Susceptible mice displayed similar data to controls in these brain areas. Interestingly, dorsal striatum (DS), brain area used as negative control, showed alterations in gene and protein expression and enzymatic activity in resilient and susceptible mice. Additionally, serum nitrate and nitrite (NOx) concentration were evaluated. Resilient mice displayed increase of systemic NOx levels when compared with susceptible animals. Concluding, our data show that prolonged social defeat stress is capable of inducing anhedonic and social approach-avoidance behaviors in adolescent male mice. Molecular tests suggest that resilience to this type of stress is associated with reduction of nNOS gene and protein expression in HC and PFC and with increase of serum NOx levels. Furthermore, molecular alterations in DS would be suggesting a role for this area in organism response to social stress.

Prenatal stress exposure (PNS) has detrimental effects on the offspring’s brain and behaviour and has been identified as an etiological factor in inducing cognitive function deficits in rodents and humans. The neural mechanisms are unclear, however reprogramming of the neuroendocrine stress axis, the hypothalamo-pituitary- adrenal (HPA) axis is hypothesised. A psychosocial stressor (residentintruder paradigm) was used to generate PNS rat offspring, making these studies clinically compatible. The hippocampus and the medial prefrontal cortex (mPFC) are critical in regulating cognitive function and also contribute to the negative feedback control of the HPA axis via corticosteroid receptors, including the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Here the Barnes maze was used to assess spatial learning and memory in male and female PNS offspring during adulthood under different scenarios, including basal and acute and chronic stress conditions. Under basal conditions, PNS was associated with reduced GR and MR mRNA expression in the medial prefrontal cortex (mPFC) and the hippocampus, respectively; suggesting inhibitory feedback control of the HPA axis may be compromised in PNS rats. Moreover, impaired spatial learning was observed in male PNS rats following acute restraint stress. Bilateral lesions of the prelimbic cortex and central administration of an MR antagonist in control rats suggested acute stress-induced learning deficits in PNS males were a result of impaired hippocampus-mediated inhibitory feedback control of the HPA axis. Conversely, a one-week variable stress regimen facilitated spatial learning in PNS rats and this was associated with elevated MR mRNA expression in the dentate gyrus. Moreover, facilitated learning in the PNS rats exposed to chronic stress could be blocked by central administration of an MR antagonist, indicating a facilitatory role of hippocampal MR in spatial learning. In summary, opposite effects of PNS on spatial learning were observed under acute and chronic stress conditions, in which hippocampal MR played a key role in regulating behavioural performance. The effect of age was also examined in PNS rats, and the findings from middle-aged (10-11 months old) rats indicated PNS may accelerate cognitive decline. Sex differences were also studied, with control females’ out-performing males under basal conditions in terms of spatial learning and behavioural flexibility; however following prenatal or chronic stress these sex differences were no longer detected. Furthermore, acute stress impaired spatial learning to a greater extent in females, and this might be attributed to greater HPA axis responses to stress in females compared with males. In conclusion, prenatal stress alters later cognitive performance, in a sex- and stress context-dependent manner. Hippocampal MR plays a critical role in mediating spatial learning, particularly during stress conditions.

Test anxiety is an individual personality trait, which results in elevated state anxiety in situations of performance evaluation. For school-age children, high-stakes examinations occurring at the culmination of programmes of study are where they frequently experience such evaluation. Alongside its impact on an individual's wellbeing, heightened test anxiety has been reliably linked to deficits in performance on examinations and assessments. Attentional bias has been shown to be an aspect of many forms of anxiety and is considered to have role in the maintenance of state anxiety, though the mechanisms underlying this are not fully clear. However, Attentional Control Theory (Eysenck, Derakshan, Santos, & Calvo, 2007) implicates preferential allocation of attention to threat in its explanation of performance deficits associated with test anxiety. The presence of attentional bias in test anxiety appears theoretically plausible with some empirical support (e.g. Putwain, Langdale, Woods and Nicholson, 2011); however, its reliability is under question. This study aims to investigate the presence of attentional bias in test anxiety, with a view to further understanding its underlying mechanisms and informing the development of interventions to ameliorate its effects. To ensure ecological validity, this study was conducted in schools and colleges, with a sample of 16-18-year olds following high-stakes programmes of study. Full investigation of test anxiety requires individuals to experience heightened state anxiety through performance evaluation threat; hence, the Trier Social Stress Test (TSST) was modified to make it applicable to this context and population. This study was conducted in two experimental phases, both of which adopted a mixed methodological approach to provide quantitative and qualitative data. The preliminary phase evaluated the materials and anxiety manipulation protocols. The main phase employed the modified-TSST in collaboration with a dot-probe task to investigate participants' attentional bias when under high performance evaluation threat. No patterns of attentional bias were uncovered to indicate a consistent relationship to either trait test anxiety or attentional control. However, there was a level of congruence between how some individuals describe themselves in evaluative situations and the attentional bias they displayed. Further investigation employing mixed methodological approaches such as Single Case Experimental Design is recommended to identify and address attentional bias in test anxiety.

Stress is known to alter immune function, both in positive and negative ways. The disparate effects of stress on immune function remains an active area of investigation. This thesis investigates how the application of social disruption stress either prior to or concurrent with infection alters the neuropathogenesis of Theiler's murine encephalitis virus. Experiment 1 verified that social disruption prior to infection exacerbated the course of infection. Experiment 2 examined application of social disruption concurrent with infection, and found that this may produce a delay in symptom onset, and possibly a protective effect. Experiment 3 directly compared the two schedules to each other. The previous findings were replicated and expanded with additional measures (both behavioral and physiological) that further verified the earlier findings. Social disruption applied prior to infection resulted in greater behavioral and physiological exacerbation of the disease. Concurrently applied stress remained protective or inhibitory in the disease progression. Timing of stress is one of several quantitative aspects of stress that has been found to impact the stress-immune interaction and should be further investigated.

Following social defeat, male hamsters exhibit behavioral changes characterized by a breakdown of normal territorial aggression and an increase in submissive/defensive behaviors in the presence of a non-aggressive intruder (NAI). We have termed this phenomenon conditioned defeat (CD). By contrast, only a small subset of defeated females exhibit submissive/defensive behavior in the presence of a NAI. We hypothesized that fluctuations in gonadal hormones might contribute to differences in the display of submissive behavior in intact female hamsters. Following social defeat, proestrous females (higher endogenous estradiol) were more likely to display conditioned defeat compared with diestrous 1 (lower endogenous estradiol) females. This finding suggests that there is an estrous cycle-dependent fluctuation in the display of CD in female hamsters and suggests that increased estradiol might contribute to increased submissive behavior. We then demonstrated that ovariectomized females given estradiol prior to CD testing exhibited significantly higher submissive behavior in the presence of a NAI suggesting that estradiol increases the expression of CD in female hamsters. We have also shown that castrated males that were singly housed for four weeks displayed significantly more submissive behavior than did their intact counterparts. Interestingly, castrated and intact males that were singly housed for 10 days prior to behavioral testing displayed similar behavior during CD testing. Together these data suggest that androgens and isolation modulate the display of CD in male hamsters. Finally, we examined brain activation following CD testing in defeated males and females (in diestrus 1 and proestrus). Defeated male and proestrous females exhibited increased Fos activation in the dorsal lateral septum and hypothalamic paraventricular nucleus relative to defeated diestrous 1 females. Diestrous 1 females exhibited increased Fos expression in the lateral bed nucleus of the stria terminalis compared with both defeated groups. Collectively, these data suggest that gonadal hormones and duration of individual housing modulate the display of CD in female and male hamsters and that those animals which display CD exhibit differences in patterns of neuronal activation than do those that do not display CD.