Alice Russell

Inflammatory biomarker profiles of mental disorders and their relation to clinical, social and lifestyle factors

In the last few decades, mental health research has increasingly provided evidence supporting the role of inflammation in pathogenesis, course and treatment of mental disorders. With such a steep incline of research, resulting in a wealth of emerged findings, it has become difficult to follow developments within the field. The present review sets out to present the recent developments and to give an overview of the inflammatory profiles of depression, psychosis and bipolar disorder, as well as variations within these disorders. Moreover, mediating factors such as social environment and childhood experience are discussed, both in terms of their potential in elucidating the complex interface between the inflammation and other closely related biological systems, as well as the possibly confounding impact of various lifestyle factors. Whilst many issues in this fascinating area of research remain to be fully understood and elaborated, all current evidence suggests that inflammation plays a key role in mental disorders and may open up novel avenues for clinical treatment.

Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression

Owing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI). Whole-blood transcriptomic analyses were conducted to investigate the following: (1) baseline gene expression differences associated with future development of IFN-α-induced depression, before IFN-α, and (2) longitudinal gene expression changes from baseline to weeks 4 or 24 of IFN-α treatment, separately in those who did and did not develop depression. Transcriptomics data were analyzed using Partek Genomics Suite (1.4-fold, FDR adjusted p⩽0.05) and Ingenuity Pathway Analysis Software. Twenty patients (34%) developed IFN-α-induced depression. At baseline, 73 genes were differentially expressed in patients who later developed depression compared with those who did not. After 4 weeks of IFN-α treatment, 592 genes were modulated in the whole sample, representing primarily IFN-α-responsive genes. Substantially more genes were modulated only in patients who developed depression (n=506, compared with n=70 in patients who did not), with enrichment in inflammation-, neuroplasticity- and oxidative stress-related pathways. A similar picture was observed at week 24. Our data indicate that patients who develop IFN-α-induced depression have an increased biological sensitivity to IFN-α, as shown by larger gene expression changes, and specific signatures both as predictors and as correlates.

Inflammation and metabolic changes in first episode psychosis: Preliminary results from a longitudinal study

Metabolic abnormalities are commonly observed in patients with psychosis, and may confer greater risk of developing cardiovascular disease later in life. Such abnormalities are associated with inflammation in the general population, and there is increasing evidence for elevated inflammation in patients with first episode psychosis (FEP). The aim of this preliminary study is to examine the effect of changes in inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), on metabolic changes in a three-month longitudinal study in a FEP sample. Fifty-three FEP patients from in- and out-patient services in South London, England, were included in this longitudinal study. Social and clinical data were collected, and fasting blood samples and anthropometric measurements (weight, Body Mass Index (BMI), lipid profile and gluco-metabolic parameters) were obtained at baseline and at three-month follow-up. Correlation analyses showed that those with increases in hsCRP over the three-month period also had increases in triglyceride levels (r=0.49, p=0.02). No association was observed with other lipid profile, or gluco-metabolic parameters, across the whole sample. Increases in weight and BMI were also associated with increases in triglyceride levels (r=0.33, p=0.02; and r=0.31, p=0.03, respectively); however, a multiple linear regression analysis found that the effects of inflammation on triglycerides were independent from the effect of changes in weight, and from the baseline inflammatory state. Our preliminary findings suggest that those patients experiencing greater increases in inflammation early on in the course of their illness may be at greater risk of developing short-term metabolic abnormalities, in particular dyslipidaemia, independent of weight-gain. Future work should investigate the use of inflammatory markers to identify patients in greater need of physical health interventions.

Depression and anxiety in patients receiving interferon-alpha: The role of illness perceptions

Development of psychiatric symptoms during interferon-alpha therapy may be influenced by psychological factors. We examined illness perceptions using the Revised Illness Perceptions Questionnaire in 55 patients with chronic hepatitis C virus infection, due to receive interferon-alpha. The Hospital Anxiety and Depression Scale was used to assess the development of symptoms. Negative identity, consequences and emotional representation beliefs were significantly associated with both higher depression and anxiety scores. Negative illness perceptions play a predictive role in the development of interferon-alpha-induced psychiatric symptoms.

Are Mood and Anxiety Disorders Inflammatory Diseases

In the last few decades there has been a growing interest in the role of psychoneuroimmunological dysfunction in neuropsychiatric disorders. This article presents recent advances in the literature, from preclinical and clinical studies, suggesting that mood and anxiety disorders are, at least in part, conditions in which the inflammatory system is activated. The evidence-base comprises alterations in the peripheral immune systems of patients with mood or anxiety disorders, together with the development of depressionand anxiety-like symptoms induced by inflammatory agents. The reported anti-inflammatory effects of current psychotropic medications as well as the efficacy of anti-inflammatory medications in treating symptoms of depression and anxiety are also reviewed. Finally, potential mechanisms mediating the link between inflammation and symptomatology presented in these neuropsychiatric illnesses are discussed as well.

Abstract # 1744 Serum factors as predictors of Interferon-alpha (IFN-alpha)-induced depression

IFN-alpha is the standard treatment for chronic hepatitis C virus (HCV) infection, which causes high rates of depression. However, the biological factors that predispose an individual to the occurrence of depression are still unknown. Previous data have reported an alteration in the serum level of inflammatory markers in depressed, when compared with non-depressed patients. There is in fact evidence for serum factors to penetrate the blood brain barrier and modulate different brain signalling. This study investigates whether co-incubation of human hippocampal progenitor cells (HPCs) with serum from IFN-alpha-treated HCV patients, collected before the treatment, differently affect cell biology, when comparing serum from patients who will and will not later develop depression. Serum samples were collected at baseline from 33 IFN-alpha-treated HCV patients. Human hippocampal progenitor cells (HPC03A/07) were co-incubated with serum samples under proliferation conditions for 48 hrs. Proliferating cells were examined by immunostaining with bromodeoxyuridine (BrdU), and apoptotic cells were evaluated with caspase 3 (CC3). Proliferating cells also expressing the apoptotic marker CC3 were defined as CC3/BrdU positive cells. Co-incubation of HPCs with serum from depressed patients significantly increased the percentage of CC3+cells ( p p

Abstract # 1785 The effects of cannabis use in interferon-alpha treatment for hepatitis C viral infection

Cannabis use in adolescence has been linked with increased risk of developing depression in adulthood and chronic cannabis use has a blunting effect on the endocannabinoid signalling. We investigated the role of cannabis use in the mechanisms underlying depression development and the impact of cannabis use on the endocannabinoid signalling in 74 patients receiving interferon-alpha treatment for hepatitis-C-viral. We measured serum endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) at baseline and treatment week 4 (TW4), using High Performance Liquid Chromatography with Tandem Mass Spectrometry. We used M.I.N.I. International Neuropsychiatric Interview to assess depression development and Cannabis Experience Questionnaire to determine cannabis use during lifetime. Our results show that the proportion of patients who smoke cannabis at baseline is 3.73 greater amongst those who develop depression during treatment compared to those who do not develop depression. When we looked at the effect of interferon-alpha on endocannabinoid levels, we found a significant increase in 2-AG levels, from baseline to TW4, only in patients who never used cannabis and those who used cannabis in the past. Levels of AEA were significantly increased from baseline to TW4 only in patients who never used cannabis. Our findings suggest that current cannabis use may increased the likelihood of developing depression during interferon-alpha treatment in hepatitis-C-viral patients. Cannabis use may have a blunting effect on eCB signaling in response to interferon-alpha treatment.