Revisiting the Basic Symptom Concept: Toward Translating Risk Symptoms for Psychosis into Neurobiological Targets

In its initial formulation, the concept of basic symptoms (BSs) integrated findings on the early symptomatic course of schizophrenia and first in vivo evidence of accompanying brain aberrations. It argued that the subtle subclinical disturbances in mental processes described as BSs were the most direct self-experienced expression of the underlying neurobiological aberrations of the disease. Other characteristic symptoms of psychosis (e.g., delusions and hallucinations) were conceptualized as secondary phenomena, resulting from dysfunctional beliefs and suboptimal coping styles with emerging BSs and/or concomitant stressors. While BSs can occur in many mental disorders, in particular affective disorders, a subset of perceptive and cognitive BSs appear to be specific to psychosis and are currently employed in two alternative risk criteria. However, despite their clinical recognition in the early detection of psychosis, neurobiological research on the aetiopathology of psychosis with neuroimaging methods has only just begun to consider the neural correlate of BSs. This perspective paper reviews the emerging evidence of an association between BSs and aberrant brain activation, connectivity patterns, and metabolism, and outlines promising routes for the use of BSs in aetiopathological research on psychosis.

Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

OBJECTIVES Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. METHODS We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. RESULTS Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=-0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=-0.05, p<0.05) and arousal (b=-0.09, p<0.05), but not with dissociation and avoidance. CONCLUSIONS The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support.

Depressive symptoms as a novel risk factor for recurrent venous thromboembolism: a longitudinal observational study in patients referred for thrombophilia investigation.

BACKGROUND Increasing evidence suggests that psychosocial factors, including depression predict incident venous thromboembolism (VTE) against a background of genetic and acquired risk factors. The role of psychosocial factors for the risk of recurrent VTE has not previously been examined. We hypothesized that depressive symptoms in patients with prior VTE are associated with an increased risk of recurrent VTE. METHODS In this longitudinal observational study, we investigated 271 consecutive patients, aged 18 years or older, referred for thrombophilia investigation with an objectively diagnosed episode of VTE. Patients completed the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). During the observation period, they were contacted by phone and information on recurrent VTE, anticoagulation therapy, and thromboprophylaxis in risk situations was collected. RESULTS Clinically relevant depressive symptoms (HADS-D score ≥ 8) were present in 10% of patients. During a median observation period of 13 months (range 5-48), 27 (10%) patients experienced recurrent VTE. After controlling for sociodemographic and clinical factors, a 3-point increase on the HADS-D score was associated with a 44% greater risk of recurrent VTE (OR 1.44, 95% CI 1.02, 2.06). Compared to patients with lower levels of depressive symptoms (HADS-D score: range 0-2), those with higher levels (HADS-D score: range 3-16) had a 4.1-times greater risk of recurrent VTE (OR 4.07, 95% CI 1.55, 10.66). CONCLUSIONS The findings suggest that depressive symptoms might contribute to an increased risk of recurrent VTE independent of other prognostic factors. An increased risk might already be present at subclinical levels of depressive symptoms.

Perception of a hectic hospital environment at admission relates to acute stress disorder symptoms in myocardial infarction patients.

OBJECTIVE Hospital crowding is a public health problem that may impact on the quality of medical treatment and increase the risk of developing traumatic stress, e.g., after myocardial infarction (MI). This study examines whether subjective appraisal of crowding at hospital admission due to MI is associated with acute stress disorder (ASD) symptoms. METHOD We investigated 102 consecutive patients with acute MI within 48h after having reached stable circulatory conditions. The appraisal of crowding was measured by the retrospective assessment of the perception of a hectic hospital environment at admission. Furthermore, patients completed the Acute Stress Disorder Scale to rate the psychological stress reaction. RESULTS The perception of a hectic hospital environment was associated with the development of ASD symptoms (r=0.254, P=.013) independently of demographic, peritraumatic and medical factors. Post hoc analysis revealed associations with dissociative (r=0.211, P=.041), reexperiencing (r=0.184, P=.074) and arousal (r=0.179, P=.083) symptoms. CONCLUSION The findings suggest that, besides objective circumstances, the way hospital admission due to MI is perceived by the patient may influence the development of MI-triggered ASD symptoms. The psychological and physiological long-term outcomes of the perception of a hectic hospital environment and the role of preventive interventions need further examination.

Subclinical Thyroid Dysfunction and Depressive Symptoms among Elderly: A Prospective Cohort Study

BACKGROUND Subclinical hypothyroidism has been associated with depressive symptoms in cross-sectional studies, but prospective data and data on subclinical hyperthyroidism are scarce. METHODS In the Leiden sub-study of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) among adults aged 70-82 years with pre-existing cardiovascular disease or known cardiovascular risk factors, TSH and free T4 levels were measured at baseline and repeated after 6 months to define persistent thyroid function status. Main outcome measures were depressive symptoms, assessed with the Geriatric Depression Scale 15 (GDS) at baseline and after 3 years. All analyses were adjusted for age, gender and education. RESULTS Among 606 participants (41% women, mean age 75 years) without anti-depressant medication, GDS scores at baseline did not differ for participants with subclinical hypothyroidism (n = 47; GDS 1.75, 95% CI 1.29-2.20, p = 0.50) or subclinical hyperthyroidism (n = 13; GDS 1.64 [0.78-2.51], p = 1.00) compared to euthyroid participants (n = 546, mean GDS 1.60 [1.46-1.73]). After 3 years, compared to euthyroid participants, change in GDS scores did not differ for participants with subclinical hypothyroidism (ΔGDS -0.03 [-0.50-0.44], p = 0.80), while subclinical hyperthyroidism was associated with an increase in GDS scores (ΔGDS 1.13 [0.32-1.93] p = 0.04). All results were similar for persistent subclinical thyroid dysfunction. CONCLUSIONS In this largest prospective study on the association of persistent subclinical thyroid dysfunction and depression, subclinical hypothyroidism was not associated with increased depressive symptoms among older adults at high cardiovascular risk. Persistent subclinical hyperthyroidism might be associated with increased depressive symptoms, which requires confirmation in a larger prospective study. © 2015 S. Karger AG, Basel.

Vaginal cytokines do not correlate with postmenopausal vulvovaginal symptoms.

OBJECTIVES Exploratory pilot study to determine the correlation between postmenopausal vulvovaginal symptoms and vaginal cytokine levels. METHODS Postmenopausal women (n = 34) not using menopausal hormone therapy and presenting with or without symptoms of vulvovaginal irritation were screened. Each participant underwent a vaginal examination and screening for vaginitis. A cervicovaginal lavage (CVL) with sterile saline and a peripheral blood sample were obtained. Main outcome measures were assessed by Luminex® X-map method on the Bio-Plex® platform. Main outcome measures were cervicovaginal and serum interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, TNF-α, GM-CSF, MIP-1-alpha and RANTES level. Cervicovaginal cytokines were adjusted to total protein concentration [pg/mcg protein]. RESULTS Twenty-six postmenopausal women were enrolled (symptomatic: n = 15; asymptomatic: n = 11). There were no significant differences between groups: age, age at menopause, vaginal pH and all CVL and serum cytokines (IL-4, IL-5, IL-10, IL-12, IL-13, TNF-α, GM-CSF, MIP-1-alpha and RANTES). GM-CSF was the most abundant vaginal cytokine (symptomatic: 146.5 ± 165.6 pg/mcg protein; asymptomatic: 146.0 ± 173.5 pg/mcg protein; p = 0.99). CONCLUSIONS Postmenopausal vulvovaginal symptoms did not correlate with vaginal inflammatory marker. There was no difference in serum or CVL cytokines between symptomatic and asymptomatic postmenopasual women. Vaginal symptoms after menopause are not related to the vaginal cytokine changes associated with loss of estrogen.

Urinary tract endometriosis in patients with deep infiltrating endometriosis: prevalence, symptoms, management, and proposal for a new clinical classification

OBJECTIVE To analyze the prevalence of urinary tract endometriosis (UTE) in patients with deep infiltrating endometriosis (DIE) and to define potential criteria for preoperative workup. DESIGN Retrospective study. SETTING University hospital. PATIENT(S) Six hundred ninety-seven patients with endometriosis. INTERVENTION(S) Excision of all endometriotic lesions. MAIN OUTCOME MEASURE(S) Correlation of preoperative features and intraoperative findings in patients with UTE. RESULT(S) Out of 213 patients presenting DIE, 52.6% suffered from UTE. In patients with ureteral endometriosis, symptoms were not specific. Among the patients with bladder endometriosis, 68.8% complained of urinary symptoms compared to 7.9% in the group of patients without UTE. In patients with rectovaginal endometriosis, the probability of ureterolysis showed a linear correlation with the size of the nodule. We found that 3 cm in diameter provided a specific cutoff value for the likelihood of ureteric involvement. CONCLUSION(S) The prevalence of UTE has often been underestimated. Preoperative questioning is important in the search for bladder endometriosis. The size of the nodule is one of the few reliable criteria in preoperative assessment that can suggest ureteric involvement. We propose a classification of ureteral endometriosis that will allow the standardization of terminology and help to compare the outcome of different surgical treatment in randomized studies.

Can urethrolysis resolve outlet obstruction related symptoms after Burch colposuspension for stress urinary incontinence?

OBJECTIVE Bladder outlet obstruction may occur after any incontinence surgery and may present as OAB, hesitancy and or the feeling of incomplete emptying. Aim of this study was to analyze the clinical and urodynamical outcome after urethrolysis in patients presenting with various clinical symptoms after Burch colposuspension for stress urinary incontinence. STUDY DESIGN Between January 2005 and December 2014, all patients who presented with symptoms and with bladder outlet obstruction were included. All patients had undergone Burch or Cowan colposuspension for stress urinary incontinence previously. Primary endpoint was the visual analogue scale (VAS) as measurement of patient perceived disease impact. Secondary endpoints were the various domains of the King's Health Questionnaire, urodynamic parameters as detrusor pressure at maximum flow, residual urine and sonographic bladder wall thickness before and six months after intervention. RESULTS Seventy-two female patients were included in this study whereof 42 suffered from urgency and urge incontinence, 20 from hesitancy and/or slow stream, seven from residual urine of more than 100ml and three from a combination of urgency and residual urine. VAS improved significantly (p<0.0001). Quality of life as determined by the King's Health Questionnaire improved for the domains general health, role limitations, emotions, physical limitations, personal limitations and incontinence impact significantly. Micturition pressure dropped significantly from 43cmH2O (95% CI 19-59cmH2O) to 18cmH2O (95% CI 16-23.5 H2O). Residual urine changed from 110ml (range 20-380ml) to 32ml (20-115ml). Bladder wall thickness decreased from 7mm (95% CI 6.235-7.152) to 5mm (95% CI 5.037-5.607; p<0.01). CONCLUSION Urethrolysis may resolve patients' symptoms and lower micturition pressure but irritative symptoms may persist.

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications

OBJECTIVES The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

Human Rhinovirus Types and Association with Respiratory Symptoms During the First Year of Life.

Human rhinoviruses (HRV) cause respiratory infections and are associated with asthma development. We assessed HRV prevalence, types and association with respiratory symptoms in the first year of life in 20 unselected infants. HRV was detected in 32% of 825 weekly nasal swabs. Seventy-four different types of all three species were identified. HRV presence and related respiratory symptoms are highly heterogeneous.

Effects of Breastfeeding on Respiratory Symptoms in Infancy.

OBJECTIVE To assess the impact of potential risk factors on the development of respiratory symptoms and their specific modification by breastfeeding in infants in the first year of life. STUDY DESIGN We prospectively studied 436 healthy term infants from the Bern-Basel Infant Lung Development cohort. The breastfeeding status, and incidence and severity of respiratory symptoms (score) were assessed weekly by telephone interview during the first year of life. Risk factors (eg, pre- and postnatal smoking exposure, mode of delivery, gestational age, maternal atopy, and number of older siblings) were obtained using standardized questionnaires. Weekly measurements of particulate matter <10 μg were provided by local monitoring stations. The associations were investigated using generalized additive mixed model with quasi Poisson distribution. RESULTS Breastfeeding reduced the incidence and severity of the respiratory symptom score mainly in the first 27 weeks of life (risk ratio 0.70; 95% CI 0.55-0.88). We found a protective effect of breastfeeding in girls but not in boys. During the first 27 weeks of life, breastfeeding attenuated the effects of maternal smoking during pregnancy, gestational age, and cesarean delivery on respiratory symptoms. There was no evidence for an interaction between breastfeeding and maternal atopy, number of older siblings, child care attendance, or particulate matter <10 μg. CONCLUSIONS This study shows the risk-specific effect of breastfeeding on respiratory symptoms in early life using the comprehensive time-series approach.

Low correlation between self-report and medical record documentation of urinary tract infection symptoms.

BACKGROUND Correlations between symptom documentation in medical records and patient self-report (SR) vary depending on the condition studied. Patient symptoms are particularly important in urinary tract infection (UTI) diagnosis, and this correlation for UTI symptoms is currently unknown. METHODS This is a cross-sectional survey study in hospitalized patients with Escherichia coli bacteriuria. Patients were interviewed within 24 hours of diagnosis for the SR of UTI symptoms. We reviewed medical records for UTI symptoms documented by admitting or treating inpatient physicians (IPs), nurses (RNs), and emergency physicians (EPs). The level of agreement between groups was assessed using Cohen κ coefficient. RESULTS Out of 43 patients, 34 (79%) self-reported at least 1 of 6 primary symptoms. The most common self-reported symptoms were urinary frequency (53.5%); retention (41.9%); flank pain, suprapubic pain, and fatigue (37.2% each); and dysuria (30.2%). Correlation between SR and medical record documentation was slight to fair (κ, 0.06-0.4 between SR and IPs and 0.09-0.5 between SR and EDs). Positive agreement was highest for dysuria and frequency. CONCLUSION Correlation between self-reported UTI symptoms and health care providers' documentation was low to fair. Because medical records are a vital source of information for clinicians and researchers and symptom assessment and documentation are vital in distinguishing UTI from asymptomatic bacteriuria, efforts must be made to improve documentation.