Dextran sulfate sodium-induced colitis in C57BL/6J mice increases their susceptibility to chronic unpredictable mild stress that induces depressive-like behavior.

AIMS: In patients with colitis, the high comorbidity of depressive disorders is well-known, but the detailed mechanisms remain unresolved. In this study, we examined whether colitis induced by dextran sulfate sodium (DSS) increased the susceptibility to chronic unpredictable mild stress (CUMS) in C57BL/6J mice with resilience to CUMS. MAIN METHODS: To induce experimental colitis and depressive-like behaviors, male 7-weeks old C57BL/6J mice were administered ad libitum 1% DSS solution for 11 days, and subjected to various mild stressors in a chronic, inevitable and unpredictable way according to a random schedule for 21 days, respectively. KEY FINDINGS: In naïve mice exposed to CUMS, their immobility times in a forced swim (FS) test were almost equal to those in control mice. The DSS administration to naïve mice induced colitis without depressive-like behavior, and at 18 days after termination of the DSS administration, the colitis had recovered to control levels, while altered diversity and composition of bacterial genera such as Bacteroides spp., Alistipes spp., etc., were found in the gut microbiota. Exposure of mice with DSS-induced colitis to CUMS (DSS + CUMS) significantly increased the immobility times in the FS test. In the gut microbiota of DSS + CUMS mice, the alteration profile of the relative abundance of bacterial genera differed from in the DSS ones. SIGNIFICANCE: These findings indicate that mice with colitis exhibit increased susceptibility to psychological stress, resulting in induction of depressive-like behavior, and this might be due, at least in part, to altered characteristics of the gut microbiota.

Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma.

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Evaluation of pain susceptibility by taking blood pressure in patients with infections: A prospective comparative study.

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.

The GABA(B1) receptor within the infralimbic cortex is implicated in stress resilience and vulnerability in mice.

Resilience is the capacity to maintain normal psychological and physical functions in the face of stress and adversity. Understanding how one can develop and enhance resilience is of great relevance to not only promoting coping mechanisms but also mitigating maladaptive stress responses in psychiatric illnesses such as depression. Preclinical studies suggest that GABA(B) receptors (GABA(B1) and GABA(B2)) are potential targets for the treatment of major depression. In this study, we assessed the functional role of GABA(B) receptors in stress resilience and vulnerability by using a chronic unpredictable stress (CUS) model in mice. As the medial prefrontal cortex (mPFC) plays a key role in the top-down modulation of stress responses, we focused our study on this brain structure. Our results showed that only approximately 41.9% of subjects exhibited anxiety- or despair-like behaviors after exposure to CUS. The vulnerable mice showed higher c-Fos expression in the infralimbic cortex (IL) subregion of the mPFC when exposed to a social stressor. Moreover, the expression of GABA(B1) but not GABA(B2) receptors was significantly downregulated in IL subregion of susceptible mice. Finally, we found that intra-IL administration of baclofen, a GABA(B) receptor agonist, rapidly relieved the social avoidance symptoms of the "stress-susceptible" mice. Taken together, our results show that the GABA(B1) receptor within the IL may play an important role in stress resilience and vulnerability, and thus open an avenue to develop novel, personalized approaches to promote stress resilience and treat stress-related psychiatric disorders.

Augmented seizure susceptibility and hippocampal epileptogenesis in a translational mouse model of febrile status epilepticus.

OBJECTIVE: Prolonged fever-induced seizures (febrile status epilepticus [FSE]) during early childhood increase the risk for later epilepsy, but the underlying mechanisms are incompletely understood. Experimental FSE (eFSE) in rats successfully models human FSE, recapitulating the resulting epileptogenesis in a subset of affected individuals. However, the powerful viral and genetic tools that may enhance mechanistic insights into epileptogenesis and associated comorbidities, are better-developed for mice. Therefore, we aimed to determine if eFSE could be generated in mice and if it provoked enduring changes in hippocampal-network excitability and the development of spontaneous seizures. METHODS: We employed C57BL/6J male mice, the strain used most commonly in transgenic manipulations, and examined if early life eFSE could be sustained and if it led to hyperexcitability of hippocampal networks and to epilepsy. Outcome measures included vulnerability to the subsequent administration of the limbic convulsant kainic acid (KA) and the development of spontaneous seizures. In the first mouse cohort, adult naive and eFSE-experiencing mice were exposed to KA. A second cohort of control and eFSE-experiencing young adult mice was implanted with bilateral hippocampal electrodes and recorded using continuous video-electroencephalography (EEG) for 2 to 3 months to examine for spontaneous seizures (epileptogenesis). RESULTS: Induction of eFSE was feasible and eFSE increased the susceptibility of adult C57BL/6J mice to KA, thereby reducing latency to seizure onset and increasing seizure severity. Of 24 chronically recorded eFSE mice, 4 (16.5%) developed hippocampal epilepsy with a latent period of ~3 months, significantly different from the expectation by chance (P = .04). The limbic epilepsy that followed eFSE was progressive. SIGNIFICANCE: eFSE promotes pro-epileptogenic network changes in a majority of C57BL/6J male mice and frank "temporal lobe-like" epilepsy in one sixth of the cohort. Mouse eFSE may thus provide a useful tool for investigating molecular, cellular, and circuit changes during the development of temporal lobe epilepsy and its comorbidities.

Vulnerability to addiction.

Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.

Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognised by the WHO as a pandemic in 2020. Host preparation to combat the virus is an important strategy to avoid COVID-19 severity. Thus, the relationship between eating habits, nutritional status and their effects on the immune response and further implications in viral respiratory infections is an important topic discussed in this review. Malnutrition causes the most diverse alterations in the immune system, suppressing of the immune response and increasing the susceptibility to infections such as SARS-CoV-2. On the other hand, obesity induces low-grade chronic inflammation caused by excess adiposity, which increases angiotensin-converting enzyme 2. It decreases the immune response favouring SARS-CoV-2 virulence and promoting respiratory distress syndrome. The present review highlights the importance of food choices considering their inflammatory effects, consequently increasing the viral susceptibility observed in malnutrition and obesity. Healthy eating habits, micronutrients, bioactive compounds and probiotics are strategies for COVID-19 prevention. Therefore, a diversified and balanced diet can contribute to the improvement of the immune response to viral infections such as COVID-19.

Relationship between Internet addiction, susceptible personality traits, and suicidal and self-harm ideation in Chinese adolescent students.

BACKGROUND AND AIMS: Internet addiction (IA) is common among young students. This study aimed to examine the influence and mechanisms of IA and susceptible personality traits on the impact of suicidal ideation in adolescent students in China. METHODS: This cross-sectional study (09/2012-09/2015) used stratified cluster sampling with "school type" for stratification; 136,266 students from 63 schools completed the questionnaire. Logistic regression analysis was performed to estimate the effect of IA (Young's Internet Addiction Test) and susceptible personality (Barratt impulsiveness scale, Buss & Perry Aggression Questionnaire; and Eysenck Personality Questionnaire-R Short Scale) on suicidal ideation (Scale of Suicidal Ideation). RESULTS: Suicidal ideation was observed in 20,218 (14.77%) of the students, and IA was detected in 28,836 (21.16%) subjects. Compared with those without IA, students with IA had a higher prevalence of suicidal ideation (P < 0.0001). No planning impulsiveness had a predictive effect on suicidal ideation in the impulsive personality trait, while in the aggressive personality trait, hostility and self-aggression had a predictive effect on suicidal ideation (all P < 0.0001). High psychoticism and neuroticism were impact factors for suicidal ideation, but extroversion was a protective factor (all P < 0.0001). DISCUSSION: These results highlight the importance of assessing personality traits and reducing IA as a possible means of lessening suicidal ideation. Susceptible personality (such as high psychoticism, high neuroticism, and low extroversion) play a prominent role in influencing the probability of having suicidal behavior among those recently exposed to IA. CONCLUSIONS: IA and susceptible personality traits were significantly correlated with suicidal and self-harm ideation among adolescent students.

Individual predictors of the susceptibility for motion-related sickness: A systematic review.

BACKGROUND: Individuals seem to be differently susceptible to motion-related sickness (motion sickness, visually induced sickness etc.). Investigations of the reasons for these different susceptibilities have revealed many potential factors that could predict individual susceptibility to motion-related sickness. OBJECTIVE: This paper attempts to conduct a comprehensive literature review on inter-individual predictors of susceptibility to motion-related sickness using systematic approaches. METHODS: After a systematic literature research, titles and abstracts of 1778 publications were screened for relevance. Reference lists of selected publications were searched for additional studies. This procedure yielded 184 relevant publications. RESULTS: The identified predictors were clustered into demographic, physiological and psychological aspects. Among these predictors, the factors gender, length of velocity storage and anxiety showed the greatest predictive power. In addition, individual susceptibility to motion-related sickness is also to a large extent dependent on the degree of habituation to the aversive stimulus. CONCLUSIONS: Some of the identified influencing factors seem to have different effects on physically and visually induced motion sickness. More research is needed to close gaps, especially on predictive factors of visually induced motion sickness.

Cardio-metabolic risk factors among young infertile women: a systematic review and meta-analysis.

BACKGROUND: There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility. OBJECTIVES: To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women. SEARCH STRATEGY: We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019). SELECTION CRITERIA: We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age. DATA COLLECTION AND ANALYSIS: At least two authors independently screened potentially eligible studies. MAIN RESULTS: There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women. CONCLUSIONS: Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction. TWEETABLE ABSTRACT: Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women.

The emergence of dyslexia in the developing brain.

Developmental dyslexia, a severe deficit in literacy learning, is a neurodevelopmental learning disorder. Yet, it is not clear whether existing neurobiological accounts of dyslexia capture potential predispositions of the deficit or consequences of reduced reading experience. Here, we longitudinally followed 32 children from preliterate to school age using functional and structural magnetic resonance imaging techniques. Based on standardised and age-normed reading and spelling tests administered at school age, children were classified as 16 dyslexic participants and 16 controls. This longitudinal design allowed us to disentangle possible neurobiological predispositions for developing dyslexia from effects of individual differences in literacy experience. In our sample, the disorder can be predicted already before literacy learning from auditory cortex gyrification and aberrant downstream connectivity within the speech processing system. These results provide evidence for the notion that dyslexia may originate from an atypical maturation of the speech network that precedes literacy instruction.

Biopsychosocial Influences on Shoulder Pain: Analyzing the Temporal Ordering of Postoperative Recovery.

Shoulder surgery is a primary intervention for shoulder pain, yet many individuals experience persistent postoperative pain. Previously, we found individuals categorized as having a high-risk phenotype (comprised of COMT variation and pain catastrophizing) had approximately double the chance of not reaching a 12-month pain recovery criterion. As a means to better understand the development of persistent postoperative shoulder pain, this study advanced our previous work by examining temporal ordering of postoperative shoulder recovery based on potential mediating factors, and expansion of outcomes to include movement-evoked pain and shoulder active range of motion. Before surgery, individuals were categorized as either high-risk (high pain catastrophizing, COMT-genotype linked to low enzyme activity [n = 41]) or low-risk (low pain catastrophizing, COMT-genotype linked to normal enzyme activity [n = 107]). We then compared potential mediating variables at 3, 6, and 12 months postoperatively 1) endogenous pain modulation defined by a conditioned pain modulation paradigm; and 2) and emotion factors such as anxiety, fear of movement, and depressive symptoms. At 3 months, the high-risk subgroup had higher fear and movement-evoked pain, and causal mediation analysis confirmed the direct effect of risk subgroup on 12-month movement evoked pain. However, baseline to 12-month change in depressive symptoms were found to mediate 53% of the total effect of risk subgroup on 12-month movement-evoked pain. This study introduces potential temporal components and relationships to the development of persistent postoperative shoulder pain, which future studies will confirm and assess for potential therapeutic targets. PERSPECTIVE: This study expands upon postoperative shoulder recovery measures to include movement-evoked pain and depressive symptoms, and provides preliminary indication of temporal ordering to postoperative shoulder recovery for a preidentified high-risk subgroup. Future studies will distinguish temporal components of shoulder surgery that may optimize treatment targets of postoperative recovery.

Anhedonia in adolescents at ultra-high risk (UHR) of psychosis: findings from a 1-year longitudinal study.

Previous findings suggested deficits in pleasure experience in schizophrenia, but little is known in psychosis risk prodrome, especially in adolescence. Aim of this study was (1) to assess anhedonia in distinct help-seeking subgroups of adolescents identified through the ultra-high risk (UHR) criteria, (2) to explore any association of anhedonia with other psychopathological aspects in the UHR group, and (3) to monitor longitudinally the stability of anhedonia in UHR individuals across 1-year follow-up period. 123 participants (13-18 years) completed the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Beck Depression Inventory-II, the Schizotypal Personality Questionnaire-Brief version, the Brief-O-LIFE questionnaire (BOL), and the Brief version of the World Health Organization Quality of Life scale (WHOQOL-BREF). Two different indexes of anhedonia were used: CAARMS "Anhedonia" item 4.3 and BOL "Introvertive Anhedonia" subscale scores. No difference in anhedonia levels between UHR and First Episode Psychosis (FEP) groups was found. UHR adolescents showed higher CAARMS and BOL anhedonia scores than non-UHR/FEP. After 1-year follow-up period, UHR adolescents had a significant decrease in severity only in CAARMS anhedonia subscores. In UHR subgroup, CAARMS anhedonia measures showed significant correlations with impaired role functioning and negative symptoms, while BOL anhedonia was significantly correlated with specific schizotypal personality traits concerning interpersonal deficits. Anhedonia is prominent in the psychosis prodrome, also in adolescence. Its severity is not statistically different from that of FEP adolescents and is related to more severe functioning impairment and a worse quality of life.

Defective spleen function in autoimmune gastrointestinal disorders.

Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria.

Neural correlates of social cognition in populations at risk of psychosis: A systematic review.

Social cognition refers to the mental operations governing social interactions. Recent research has highlighted the importance of social cognition in determining functional outcome in patients with schizophrenia and in psychosis risk populations. The aim of this review is to investigate the neural correlates of social cognition in different psychosis risk populations, potentially representing different levels of risk i.e. high schizotypy (SR), familial risk (FR) and clinical high risk (CHR). PsychINFO, Web of Science and PubMed were systematically searched, and 39 papers were included in the final review. Results in FR samples were highly inconclusive. In SR samples, findings showed a tendency towards increased task related activity in frontal cortex regions. The most consistent results come from CHR samples, where findings suggest increased task related activity in frontal and cingulate cortices. Interestingly, all studies of CHR populations also report increased activity in temporal cortex and abnormal response to neutral stimuli during emotional processing tasks. These findings are discussed in relation to dopamine models of psychosis due to temporal cortex abnormality.

Enhanced methamphetamine-induced conditioned place preference in risk-taking rats.

Patients with psychiatric disorders, such as gambling and substance use, tend to exhibit maladaptive decision-making. In this study, we assessed individual differences in risk-taking behaviors using a rat gambling task (GT) and investigated the relationship between risk-taking behaviors and vulnerability to drug dependence using methamphetamine (METH)-induced conditioned place preference (CPP). In the GT using a radial arm maze, male Long-Evans rats were trained to choose one of three choice arms (a low-risk/low reward (L-L), a high-risk/high reward (H-H), and an empty arm) in 16 trials per day for 14 days. METH-induced CPP consisted of 6 sessions: habituation, conditioning, preference test (Test I), extinction, extinction test (Test II), and reinstatement test (Test III). Results demonstrated that the percentage of choosing the H-H arm was significantly positively correlated with the percentage of time spent in the METH-paired compartment in the preference test, but not with the extinction and reinstatement tests, suggesting that risk-taking rats are more vulnerable to drug dependence.

Combining quantitative susceptibility mapping to the morphometric index in differentiating between progressive supranuclear palsy and Parkinson's disease.

PURPOSE: To determine whether the susceptibility value in the deep gray matter obtained by quantitative susceptibility mapping (QSM) provides additive value to the morphometric index for differentiating progressive supranuclear palsy (PSP) from Parkinson's disease (PD). MATERIALS AND METHODS: PSP- (n = 8) and PD patients (n = 18) and 18 age-matched healthy controls who underwent QSM and 3D magnetization-prepared rapid gradient echo (MPRAGE) sequences. The mean susceptibility values (MSVs) of the deep gray matter structures on QSM- and areas of the midbrain (morphometric index, MI) on 3D MPRAGE images were measured by two neuroradiologists. Analysis of variance, the Scheffe test and receiver operating characteristic (ROC) analysis were conducted to assess differences and discriminate among PSP, PD and controls by the MSVs and the MI. Using the MSV of a structure with the best area under the curve (AUC) and the MI, we created a decision tree to differentiate between PSP and PD. RESULTS: The MSVs of the globus pallidus (GP) and substantia nigra (SN) were significantly higher in PSP than PD and the controls (p < .05). By ROC analysis (PSP vs PD), AUC was greatest (0.903) for the GP. The MI was significantly smaller in PSP than PD and the controls (p < .05); AUC (PSP vs PD) was 0.917. The decision tree using cutoff values of 244 parts per billion for MSV of the GP and 74.0 mm2 for MI served to completely differentiate between PSP and PD. CONCLUSION: The MSV in the GP on QSM images adds value to the MI for differentiating PSP from PD.

Out in the cold and sick: low temperatures and fungal infections impair a frog's skin defenses.

Amphibians worldwide continue to battle an emerging infectious disease, chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd). Southern leopard frogs, Rana sphenocephala, are known to become infected with this pathogen, yet they are considered 'of least concern' for declines due to chytridiomycosis. Previous studies have shown that R. sphenocephala secretes four antimicrobial peptides (AMPs) onto their skin which may play an important role in limiting susceptibility to chytridiomycosis. Here, we examined (1) the effects of temperature and AMP depletion on infections with Bd and (2) the effects of temperature and Bd infection on the capacity to secrete AMPs in juvenile leopard frogs. Pathogen burden and mortality were greater in frogs exposed to Bd at low temperature but did not increase following monthly AMP depletion. Both low temperature and Bd exposure reduced the capacity of juvenile frogs to restore peptides after monthly depletions. Frogs held at 14°C were poorly able to restore peptides in comparison with those at 26°C. Frogs held at 26°C were better able to restore their peptides, but when exposed to Bd, this capacity was significantly reduced. These results strongly support the hypothesis that both colder temperatures and Bd infection impair the capacity of juvenile frogs to produce and secrete AMPs, an important component of their innate defense against chytrid fungi and other pathogens. Thus, in the face of unpredictable climate changes and enzootic pathogens, assessments of disease risk should consider the potential for effects of environmental variation and pathogen exposure on the quality of host defenses.