Major depressive disorder (MDD) is common among college students. The disease perpetuates depressive symptoms and potentially leads to chronic depressive episodes. Existing literature has shown that students who use both cognitive and behavioral maladaptive coping skills are more prone to endure depressive symptoms and poorer academic performance. Despite these known associations, little research has examined the relationship between coping skills and self-efficacy in response to warning signs of MDD in college students. This study sought to fill the gaps in the research of MDD related to precursors, predictors, and coping mechanisms among undergraduate students in a national sample of U.S. college students. Secondary data (N = 6,713) were analyzed from the Healthy Minds Study 2012, which used the Patient Health Questionnaire-9 (PHQ-9) with a test-retest reliability. Social learning and social cognitive theories were used as the theoretical frameworks to focus on problems such as management of life activities, academic success, and maladaptive beliefs. Analyses of the data from the cross-sectional survey using multiple linear and logistic regressions indicated a statistically significant relationship between depressive symptoms and the potential predictive factors of MDD. These findings contribute positively to social change by informing the work of therapists and program developers, who may use these results to create programs that reduce depressive symptoms among undergraduates.

This study investigated the utility of the Personality Assessment Inventory (PAI) for diagnosing and discriminating between Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) with university counseling center clients. Participants were 1541 male and female students who received services at a student counseling center at a large university. Participants were classified as MDD, GAD, or Other Diagnosis (OD) based on the diagnosis determined by the treating clinician, and PAI profiles were compared between the three groups. The PAI Structural Summary-Revised contains Diagnostic Consider Clusters (DCC) that were designed to identify PAI scales/subscales that are typically elevated or suppressed when a particular disorder is present. The DCC’s for MDD and GAD were examined and the results demonstrated that the criteria for the DCC for MDD were met by 2.2% of the MDD group, and the criteria for the DCC for GAD were met by 3.8% of the GAD group. A discussion of these findings is offered, and the appropriateness of using the DCC’s for the purpose of diagnosis with any population is questioned. Additionally, DCC’s for MDD and GAD for use with university counseling center clients are proposed. Finally, discriminant analysis (DA) was employed to develop various discriminant functions that can be used to classify individual PAI profile data into specific diagnostic groups. In particular, one discriminant function was created that is capable of examining any PAI profile, and classifying it as either MDD or OD. A second discriminant function was produced that can analyze any PAI profile and categorize it as either GAD or OD. The final discriminant function was developed to evaluate a PAI profile that represents either MDD or GAD and determine which diagnosis is appropriate. Each discriminant function was shown to accurately predict the associated diagnoses. A discussion of the various predictor variables is offered. Taken together, these results support the use of the PAI for diagnosing and discriminating between MDD and GAD with university counseling center clients.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

No description available.

Background: Patients with borderline personality disorder (BPD) suffer from instability of their relationships, their affectivity and their identity. The purpose of the study was to investigate negative affects and identity disturbance in patients with BPD and in patients without personality disorder using questionnaire data and interview data. Sampling and Methods: Twelve patients with BPD and 12 patients with major depressive disorder without any personality disorder were assessed with the Structured Interview of Personality Organization (STIPO) and questionnaires (Inventory of Personality Organization, Beck Depression Inventory, State-Trait Anxiety Inventory). They were compared with respect to the frequency of negative affective verbal expressions using computerized content analysis methods. Results: BPD patients showed higher levels of anxiety, depression and identity diffusion in the questionnaires than major depressive disorder patients without personality disorder. However, they did not report more negative affective expressions in the interview. Patients with identity disturbance of both groups showed higher values of negative mood in the questionnaires, but less anger, less anxiety and less affective intensity in the interview. Conclusion: The preliminary findings indicate that patients with identity disturbance show high levels of negative affects in questionnaires but only few negative affects in the interview situation. More studies are needed to enhance the understanding of negative affects and identity disturbance in BPD. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Patients with MDD demonstrate impairments in various components of affective processing, which are believed to persist in the remitted phase of the illness and are believed to underlie the vulnerability for future relapse. Despite advances in neuropsychiatry, the neuroanatomical site of action of various treatment modalities remains unclear, leaving clinicians without an algorithm to guide optimal treatment selection for individual patients. This thesis sought to characterize differences in brain activation during affective processing between MDD treatment responders (RS) and non-responders (NR) by combining clinical and neuroimaging variables in a repeat-measure functional magnetic resonance imaging (fMRI) investigation. We induced increases in positive and negative affect using visual stimuli under fMRI conditions in 21 MDD subjects and 18 healthy controls (HC). Based on previous neuroimaging investigations and preclinical animal data, we hypothesized that increased activation of the amygdala and the pregenual cingulate during negative affect induction (NAI), and decreased activity of the ventral striatum during positive affect induction (PAI), would differentiate ultimate NR from RS. Following the first scan, treatment with fluoxetine and olanzapine was initiated in the MDD group, with follow-up scans at one- and six-weeks thereafter. We hypothesized that decreases in depressive symptoms would be associated with decreased activation of the ventromedial prefrontal cortex (PFC) and amygdala during NAI and increased activation of the hippocampus during PAI. Eleven MDD subjects met criteria for clinical remission at study endpoint. Based on trait differences between MDD and HC, we hypothesized that differences observed during NAI would be limited to brain regions involved in regulation of the affective state, including the dorsolateral PFC and the anterior midcingulate cortex. The results of the analyses confirmed the a-prior hypotheses and additionally demonstrated differential activation of the insular, medial temporal, and premotor cortex during repeat PAI and NAI between HC, RS, and NR. These findings provide: i) a neuroanatomical target of successful antidepressant therapy during PAI/NAI; ii) a differential effect of depressive symptoms and dispositional affect on brain activation during PAI/NAI; and iii) an a-prior method to differentiate RS from NR, and iv) demonstrate the need for additional treatment to prevent relapse in the remitted state.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Depression is common in haemodialysis (HD) patients and is often unrecognised and undertreated, though associated with excess morbidity and mortality. Diagnosis is challenging due to symptom overlap with kidney failure, with fatigue being the most common overlapping symptom. Research on the effectiveness of antidepressant medication in this setting is sparse. A recent systematic review advocated well-designed Randomised Controlled Trials (RCTs) in this setting. The studies reported in this thesis had a number of aims. The main aim was to undertake a multicentre feasibility randomised, double blind, placebo-controlled trial of sertraline in patients on HD with Major Depressive Disorder (MDD). To identify suitable patients for this, a screening phase was required, which also allowed determination of the prevalence of depression in this setting and of the relative effectiveness of screening tools Patient Health Questionnaire-2 (PHQ-2), Patient Health Questionnaire-9 (PHQ-9), and Beck Depression Inventory-II (BDI-II). It also allowed examination of the relationships of fatigue in this setting (assessed mainly by the Multidimensional Fatigue Inventory (MFI), including those with a diagnosis, and management of depression. The finding, during screening, that a large proportion of the HD cohort was already on antidepressant treatment, presented the opportunity to study 'real-life' practice patterns in the management of antidepressant treatment in this setting. Recruitment into the RCT was difficult. 1,355 patients in five HD centres were considered for screening, but 243 of these were excluded, mainly because of their inability to read and understand English. Of the remaining 1,110 patients, 709 consented to screening. 231 of these screened positive for high depression symptoms but 130 were not considered for the trial phase, mainly because of concurrent treatment for depression (68 patients), and other contraindicated conditions and medication. In addition, 38 patients declined to take part in the psychiatric interview necessary for diagnosis of MDD. Of the 63 who underwent the diagnostic interview, 37 (58.7%) were diagnosed with MDD and 30 consented to enter the RCT and were randomised into sertraline or placebo groups. This was half of the anticipated recruitment into the RCT. Twenty-one patients (70%) completed the six-month study, eight of 15 in the sertraline group and 13 of 15 in the placebo group (p < 0.05). Drop out was mainly due to adverse or serious adverse events. Depression scores (BDI-II and Montgomery-Åsberg Depression Rating Scale (MADRS)) improved significantly in both the sertraline and placebo groups over six months but there were no significant differences between the treatment groups. There was a slight suggestion of more rapid improvement over the first two months on sertraline, but this was not significant. Fatigue scores were high in all sub-domains - with only a weak relationship with age and comorbidity. Mental fatigue was the strongest independent predictor of high depressive symptoms (BDI-II ≥16, PHQ-9 ≥8), while physical fatigue had the strongest relationship with dialysis recovery time, and survival. Distinguishing between these components of fatigue may have a role in refining the diagnosis and management of MDD. Forty-one of the 76 patients on antidepressant medication at screening were followed up for a mean of 14±5 months. Ten different antidepressant agents were being taken - the most common being Citalopram (39%). Most had been prescribed by GPs. Two-thirds of patients either deteriorated or failed to improve in terms of BDI-II scores during follow-up, many of whom had had no adjustment of medication during this time. Diagnostic evaluation at follow-up showed 37% to be suffering from current or recurrent major depressive episodes (MDE), 48% to have evidence of past MDE, and 15% to have no evidence of ever having been depressed. These empirical studies confirm that depression is very common in HD patients. Its diagnosis is complicated due to symptom overlap with the uraemic syndrome. Fatigue seems to be a key area of overlap with symptoms of depression with a complex relationship. There was no obvious benefit from antidepressants in this feasibility RCT and there was a high drop-out rate due to adverse events, particularly in the sertraline group. These findings raise concerns about the benefits and risks of antidepressants in patients on HD. Current practice patterns may be subjecting patients to substantial risk for little or no benefit. Identifying whether antidepressant medication is effective in this context is a major clinical need, hence the requirement for a definitive study. There is no doubt that to undertake a definitive study would pose considerable recruitment challenges. The findings presented here emphasise the importance of finding ways to overcome these challenges that might include efforts to incorporate patients already taking antidepressants.

Over the last decade there has been a great effort to annotate noncoding regions of the genome, particularly those that regulate gene expression. These regulatory elements contain binding sites for transcription factors (TF), which interact with one another and transcriptional machinery to initiate, enhance, or repress gene expression. The Encyclopedia of DNA Elements (ENCODE) consortium has generated thousands of epigenomic datasets, such as DNase-seq and ChIP-seq experiments, with the goal of defining such regions. By integrating these assays, we developed the Registry of candidate Regulatory Elements (cREs), a collection of putative regulatory regions across human and mouse. In total, we identified over 1.3M human and 400k mouse cREs each annotated with cell-type specific signatures (e.g. promoter-like, enhancer-like) in over 400 human and 100 mouse biosamples. We then demonstrated the biological utility of these regions by analyzing cell type enrichments for genetic variants reported by genome wide association studies (GWAS). To search and visualize these cREs, we developed the online database SCREEN (search candidate regulatory elements by ENCODE). After defining cREs, we next sought to determine their potential gene targets. To compare target gene prediction methods, we developed a comprehensive benchmark of enhancer-gene links by curating ChIA-PET, Hi-C and eQTL datasets. We then used this benchmark to evaluate unsupervised linking approaches such as the correlation of epigenomic signal. We determined that these methods have low overall performance and do not outperform simply selecting the closest gene. We then developed a supervised Random Forest model which had notably better performance than unsupervised methods. We demonstrated that this model can be applied across cell types and can be used to predict target genes for GWAS associated variants. Finally, we used the registry of cREs to annotate variants associated with psychiatric disorders. We found that these "psych SNPs" are enriched in cREs active in brain tissue and likely target genes involved in neural development pathways. We also demonstrated that psych SNPs overlap binding sites for TFs involved in neural and immune pathways. Finally, by identifying psych SNPs with allele imbalance in chromatin accessibility, we highlighted specific cases of psych SNPs altering TF binding motifs resulting in the disruption of TF binding. Overall, we demonstrated our collection of putative regulatory regions, the Registry of cREs, can be used to understand the potential biological function of noncoding variation and develop hypotheses for future testing.