Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

BACKGROUND The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. METHODS In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. RESULTS At baseline, 54.3 % of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4 %. Depressive, obsessive-compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive-compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. CONCLUSION Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive-compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

Evaluation of association between childhood obesity and depression: A systematic literature review

Obesity has become a major public health concern throughout the world. Both developing as well as developed countries have been facing the consequences of obesity. [1, 2] According to World Health Organization, worldwide prevalence of overweight among adults was 1.6 billion and that of obesity was 400 million by the end of year 2005. At the same time, around 20 million children of less than 5 years of age were overweight worldwide. [3] ^ From amongst the obese children, around 15% of children manifest symptoms of depression before 18 years of age as compared to non-obese children of the same age group. Approximately 3-5% of these obese individuals develop major depressive disorders (MDD). [4, 5] The incidence of depression increases markedly as the child reaches puberty. The risk of persistent depression in childhood as well as in adulthood is two to four times higher if the child is obese as compared to those depressed adult individuals who are not obese in their childhood. [6, 7] ^ This paper will review the scientific literature concerning the association between childhood obesity and depression. ^

THE EFFECT OF PERSON-ENVIRONMENT INTERACTION ON ANXIETY, DEPRESSION, AND SUBJECTIVE DISTRESS OF OPTOMETRY STUDENTS

The purpose of this study was to investigate whether an incongruence between personality characteristics of individuals and concomitant charcteristics of health professional training environments on salient dimensions contributes to aspects of mental health. The dimensions examined were practical-theoretical orientation and the degree of structure-unstructure. They were selected for study as they are particularly important attributes of students and of learning environments. It was proposed that when the demand of the environment is disparate from the proclivities of the individual, strain arises. This strain was hypothesized to contribute to anxiety, depression, and subjective distress.^ Select subscales on the Omnibus Personality Inventory (OPI) were the operationalized measures for the personality component of the dimensions studied. An environmental index was developed to assess students' perceptions of the learning environment on these same dimensions. The Beck Depression Inventory, State-Trait Anxiety Inventory and General Well-Being schedule measured the outcome variables.^ A congruence model was employed to determine person-environment (P-E) interaction. Scores on the scales of the OPI and the environmental index were divided into high, medium, and low based on the range of scores. Congruence was defined as a match between the level of personality need and the complementary level of the perception of the environment. Alternatively, incongruence was defined as a mismatch between the person and the environment. The consistent category was compared to the inconsistent categories by an analysis of variance procedure. Furthermore, analyses of covariance were conducted with perceived supportiveness of the learning environment and life events external to the learning environment as the covariates. These factors were considered critical influences affecting the outcome measures.^ One hundred and eighty-five students (49% of the population) at the College of Optometry at the University of Houston participated in the study. Students in all four years of the program were equally represented in the study. However, the sample differed from the total population on representation by sex, marital status, and undergraduate major.^ The results of the study did not support the hypotheses. Further, after having adjusted for perceived supportiveness and life events external to the learning environment, there were no statistically significant differences between the congruent category and incongruent categories. Means indicated than the study sample experienced significantly lower depression and subjective distress than the normative samples.^ Results are interpreted in light of their utility for future study design in the investigation of the effects of P-E interaction. Emphasized is the question of the feasibility of testing a P-E interaction model with extant groups. Recommendations for subsequent research are proposed in light of the exploratory nature of the methodology. ^

Associations between exposure to violence and depression in 5th grade students: Results from the Healthy Passages study

Purpose. To describe the prevalence of violence exposure and depression and their association among 5th grade students. ^ Methods.. Students (n=5,147) attending 5th grade (mean age 11.12) from three major metropolitan areas in the United States were surveyed on various health-related measures including experience with being a victim of violence (adapted from YRBS and Traumatic Events Screening Inventory) and depressive symptoms (from the DISC Predictive Scale). Prevalence was calculated for rates of violence exposure as well as depression defined as having five or more depressive symptoms. Logistic regression was used to examine the association between exposure to violence and depression. ^ Results. This study found that over 35% of students were exposed to some form of violence such as being threatened, hit, punched, kicked, beaten up, or threatened/injured with a gun or knife. Male students had a higher prevalence than female students on almost all exposure types. Over 7% of students also reported having 5 or more depressive symptoms. All forms of violence were significantly associated with depression. Students who had been a victim of violence were between 2.5 and 6.5 more likely to have five or more depression symptoms. Conslusion. The results of this study underscore the urgent need of collaborative prevention and treatment efforts for children exposed to violence. By preventing such exposure, serious effects including physical injury, mental health problems, and other detrimental outcomes may be mitigated.^

Relative phase shift and oscillation observations at moorings in the Filchner Depression area

Properties of the dense ice shelf water plume emerging from the Filchner Depression in the southwestern Weddell Sea are described, using available current meter records and CTD stations. A mean hydrography, based on more than 300 CTD stations gathered over 25 yr points to a cold, relatively thin and vertically well-defined plume east of the two ridges cross-cutting the continental slope about 60 km from the Filchner sill, whereas the dense bottom layer is warmer, more stratified and much thicker west of these ridges. The data partly confirm the three major pathways suggested earlier and agree with recent theories on topographic steering by submarine ridges. A surprisingly high mesoscale variability in the overflow region is documented and discussed. The variability is to a large extent due to three distinct oscillations (with periods of about 35 h, 3 and 6 d) seen in both temperature and velocity records on the slope. The oscillations are episodic, barotropic and have a horizontal scale of ~20-40 km across the slope. They are partly geographically separated, with the longer period being stronger on the lower part of the slope and the shorter on the upper part of the slope. Energy levels are lower west of the ridges, and in the Filchner Depression. The observations are discussed in relation to existing theories on eddies, commonly generated in plumes, and continental shelf waves.

Complexity analysis of spontaneous brain activity: effects of depression and antidepressant treatment

Magnetoencephalography (MEG) allows the real-time recording of neural activity and oscillatory activity in distributed neural networks. We applied a non-linear complexity analysis to resting-state neural activity as measured using whole-head MEG. Recordings were obtained from 20 unmedicated patients with major depressive disorder and 19 matched healthy controls. Subsequently, after 6 months of pharmacological treatment with the antidepressant mirtazapine 30 mg/day, patients received a second MEG scan. A measure of the complexity of neural signals, the Lempel–Ziv Complexity (LZC), was derived from the MEG time series. We found that depressed patients showed higher pre-treatment complexity values compared with controls, and that complexity values decreased after 6 months of effective pharmacological treatment, although this effect was statistically significant only in younger patients. The main treatment effect was to recover the tendency observed in controls of a positive correlation between age and complexity values. Importantly, the reduction of complexity with treatment correlated with the degree of clinical symptom remission. We suggest that LZC, a formal measure of neural activity complexity, is sensitive to the dynamic physiological changes observed in depression and may potentially offer an objective marker of depression and its remission after treatment.

Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons

Cerebellar Purkinje neurons receive two major excitatory inputs, the climbing fibers (CFs) and parallel fibers (PFs). Simultaneous, repeated activation of CFs and PFs results in the long-term depression (LTD) of the amplitude of PF-evoked synaptic currents. To induce LTD, activation of CFs may be substituted with depolarization of the Purkinje neuron to turn on voltage-activated calcium channels and increase the intracellular calcium concentration. The role of PFs in the induction of LTD, however, is less clear. PFs activate glutamate metabotropic receptors that increase phosphoinositide turnover and elevate cytosolic inositol 1,4,5-trisphosphate (InsP3). It has been proposed that calcium release from intracellular stores via InsP3 receptors may be important in the induction of LTD. We studied the role of InsP3 in the induction of LTD by photolytic release of InsP3 from its biologically inactive “caged” precursor in voltage-clamped Purkinje neurons in acutely prepared cerebellar slices. We find that InsP3-evoked calcium release is as effective in LTD induction as activation of PFs. InsP3-induced LTD was prevented by calcium chelator 1,2-bis(2-amino phenoxy)ethane-N,N,N′,N′-tetraacetic acid. LTD produced either by repeated activation of PFs combined with depolarization (PF+ΔV), or by InsP3 combined with depolarization (InsP3+ΔV) saturated at ≈50%. Maximal LTD induced by PF+ΔV could not be further increased by InsP3+ΔV and vice versa, which suggests that both protocols for induction of LTD share a common path. In addition to inducing LTD, photo-release of InsP3+ΔV resulted in the rebound potentiation of inhibitory synaptic currents. In the presence of heparin, an InsP3 receptor antagonist, repeated activation of PF+ΔV failed to induce LTD, suggesting that InsP3 receptors play an important role in LTD induction under physiological conditions.

Age-specific inbreeding depression and components of genetic variance in relation to the evolution of senescence.

Two major theories of the evolution of senescence (mutation accumulation and antagonistic pleiotropy) make different predictions about the relationships between age, inbreeding effects, and the magnitude of genetic variance components of life-history components. We show that, under mutation accumulation, inbreeding decline and three major components of genetic variance are expected to increase with age in randomly mating populations. Under the simplest version of the antagonistic pleiotropy model, no changes in the severity of inbreeding decline, dominance variance, or the genetic variance of chromosomal homozygotes are expected, but additive genetic variance may increase with age. Age-specific survival rates and mating success were measured on virgin males, using lines extracted from a population of Drosophila melanogaster. For both traits, inbreeding decline and several components of genetic variance increase with age. The results are consistent with the mutation accumulation model, but can only be explained by antagonistic pleiotropy if there is a general tendency for an increase with age in the size of allelic effects on these life-history traits.

Anxiety and depression symptoms in liver encephalopathy : are they psychiatric or organic?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Prospective longitudinal study of subcortical brain volumes in individuals at high familial risk of mood disorders with or without subsequent onset of depression

Subcortical volumetric brain abnormalities have been observed in mood disorders. However, it is unknown whether these reflect adverse effects predisposing to mood disorders or emerge at illness onset. Magnetic resonance imaging was conducted at baseline and after two years in 111 initially unaffected young adults at increased risk of mood disorders because of a close family history of bipolar disorder and 93 healthy controls (HC). During the follow-up, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the others remaining well (HR-well). Volumes of the lateral ventricles, caudate, putamen, pallidum, thalamus, hippocampus and amygdala were extracted for each hemisphere. Using linear mixed-effects models, differences and longitudinal changes in subcortical volumes were investigated between groups (HC, HR-MDD, HR-well). There were no significant differences for any subcortical volume between groups controlling for multiple testing. Additionally, no significant differences emerged between groups over time. Our results indicate that volumetric subcortical brain abnormalities of these regions using the current method appear not to form familial trait markers for vulnerability to mood disorders in close relatives of bipolar disorder patients over the two-year time period studied. Moreover, they do not appear to reduce in response to illness onset at least for the time period studied.

WHOQOL-BREF as a measure of quality of life in older patients with depression

Objective: To assess the reliability and validity of a brief measure of quality of life recently developed by the World Health Organization, the WHOQOL-BREF, and to examine its association with a variety of clinical and sociodemographic factors in older depressed patients. Design: Cross-sectional study. Methods: Older depressed patients (N=41) underwent diagnostic assessment using the Composite International Diagnostic Interview (CIDI) and were independently assessed on a variety of measures including the WHOQOL-BREF (a 26-item self-report questionnaire generating four domain scores), Hamilton Depression Rating Scale (HAM-D); Geriatric Depression Scale (GDS); Mini-mental State Examination (MMSE); Modified Barthel Index (MBI); Instrumental activities of daily living (IADL), and measures of physical health status and social relationships. Estimates of inter-rater and test-retest reliability, and concurrent validity were made. Results: 39 subjects completed the study. The majority of subjects (94.9%) received a diagnosis of DSM-IV Major Depressive Disorder. Levels of comorbidity were high. Three of the four domains of the WHOQOL-BREF (Physical, Psychological and Environment domains) demonstrated satisfactory reliability and validity. However, the Social Relationships domain exhibited poor validity. Quality of life scores were strongly correlated with severity of depression, number of self-reported physical symptoms and self-assessed general health status. There was no relationship between diagnostic comorbidity and quality of life scores. Conclusions: The WHOQOL-BREF was successfully administered to older depressed patients although the concurrent validity of one of its four domains was poor. Quality of life scores were strongly correlated with severity of depression, raising the issue of measurement redundancy.

Adolescents' reactions to universal and indicated prevention programs for depression: Perceived stigma and consumer satisfaction

There is a common view that one of the major considerations in selecting between universal and indicated interventions is the marked stigma produced by the latter. However, to date there has been no empirical examination of this assumption. The current study examined reported stigma and program satisfaction following two school-based interventions aimed at preventing depression in 532 middle adolescents. The interventions were conducted either across entire classes by classroom teachers (universal delivery) or in small high risk groups by mental health professionals (indicated delivery). The indicated delivery was associated with significantly greater levels of perceived stigma, but effect sizes were small and neither program was associated with marked stigma in absolute terms. Perceived stigma was more strongly associated with aspects of the individual including being male and showing greater externalizing symptomatology. In contrast, the indicated program was evaluated more positively by both participants and program leaders and effect sizes for these measures of satisfaction were moderate to large. The results point to the need for further empirical evaluation of both perceived stigma and program satisfaction in providing balanced considerations of the value of indicated and universal programs.

Cognitive change process during group cognitive behaviour therapy for depression

Background: This study extended that of Kwon and Oei [Kwon, S.M., Oei, T.P.S., 2003. Cognitive change processes in a group cognitive behavior therapy of depression. J. Behav. Ther. Exp. Psychiatry, 3, 73-85], which outlined a number of testable models based on Beck's cognitive theory of depression. Specifically, the current study tested the following four competing models: the causal, consequential, fully and partially interactive cognitive models in patients with major depressive disorder. Methods: A total of 168 clinically depressed outpatients were recruited into a 12-week group cognitive behaviour therapy program. Data was collected at three time points: baseline, mid- and at termination of therapy using the ATQ DAS and BD1. The data were analysed with Amos 4.01 (Arbuckle, J.L., 1999. Amos 4.1. Smallwaters, Chicago.) structural equation modelling. Results: Results indicated that dysfunctional attitudes, negative automatic thoughts and symptoms of depression reduced significantly during treatment. Both the causal and consequential models equally provided an adequate fit to the data. The fully interactive model provided the best fit. However, after removing non-significant pathways, it was found that reduced depressive symptom contributed to reduced depressogenic automatic thoughts and dysfunctional attitudes, not the reverse. Conclusion: These findings did not fully support Beck's cognitive theory of depression that cognitions are primary in the reduction of depressed mood. (c) 2006 Elsevier B.V. All rights reserved.

Elevated amygdala activity to sad facial expressions:a state marker of bipolar but not unipolar depression

Background - Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Methods - Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. Results - The BDd—relative to HC, BDr, and MDD—showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Conclusions - Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.