UNCORRECTED PROOF Psychiatry Research xxx (2017) xxx-xxx Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com Associations between severity of anxiety and clinical and biological features of major affective disorders Fernanda Liboni Cavicchioli a , Michael Maes a, b, c, d, ⁎ , Chutima Roomruangwong b , Kamila Landucci Bonifacio a , Decio Sabbatini Barbosa a , George Anderson e , Heber Odebrecht Vargas a , Sandra Odebrecht Vargas Nunes a a Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Brazil b Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand c Impact Strategic Research Center, Deakin University, Geelong, Australia d Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria e CRC, Scotland and London, UK ARTICLE INFO Keywords: Bipolar disorder Depressive disorder Anxiety disorders Comorbidity HDL-cholesterol Metabolic syndrome Lithium ABSTRACT Patients with major affective disorders (MAFD) with comorbid anxiety show a greater functional impairment than those without anxiety. The aim of this study is to delineate the associations between severity of anxi- ety in MAFD, namely bipolar disorder (BD) and major depression (MDD), and MAFD characteristics and serum high-density lipoprotein (HDL)-cholesterol levels. Recruited were 82 participants with anxiety disoders and 83 without anxiety disoders, including 101 MAFD patients and 51 healthy controls. We used the Hamilton Anxiety Rating Scale (HAM-A) to measure severity of anxiety and made the diagnoses of posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD) and pho- bias. The HAM-A score is significantly predicted by higher number of depressive episodes, GAD and phobias, childhood trauma, tobacco use disorder, metabolic syndrome and lowered HDL-cholesterol. Increased HAM-A scores are, independently from severity of depression, associated with lowered quality of life, increased disabil- ities and suicidal ideation. Lithium treatment significantly lowers HAM-A scores. It is concluded that severity of anxiety significantly worsens the phenomenology of MAFD. Therefore, treatments of MAFD should target in- creased severity of anxiety and its risk factors including low HDL-cholesterol, metabolic syndrome, childhood trauma and tobacco use disorder. 1. Introduction Anxiety and mood disorders are frequently comorbid and this co-oc- currence indicates a more severe course and outcome (Merikangas et al., 2007). In 1994, Maes et al. (1994b) showed that major depression (MDD) may be divided into two distinct classes, namely major depres- sion with and without anxiety features. Among patients with MDD, the 12-month prevalence of comorbid anxiety is 57.5% and the lifetime prevalence 59.2% (Culpepper et al., 2008; Fava et al., 2000). Comorbid anxiety disorders in MDD include social phobia (27.0%), simple pho- bia (16.9%), panic disorder (PD) (14.5%), generalized anxiety disorder (GAD) (10.6%), obsessive-compulsive disorder (OCD) (6.3%) and ago- raphobia (5.5%) (Fava et al., 2000). Some authors regard GAD as be longing to the MDD / stress disorders spectrum (Mennin et al., 2008). Following traumatic events, there is a strong co-occurrence of post-trau- matic stress disorder (PTSD) and MDD (Maes et al., 2000). In bipolar disorder (BD), it is estimated that comorbid anxiety disorders occur in approximately 75% of individuals (American Psychiatric Association, 2013; Hawke et al., 2013), frequent disorders being social phobia, spe- cific phobias, PD, PTSD and GAD (Hawke et al., 2013; Nabavi et al., 2015; Otto et al., 2004). There is a strong co-occurrence of specific pho- bias (10.8%), social phobias (13.3%), PD (16.8%), PTSD (10.8%) and OCD (10.7%) in BD (Annigeri et al., 2011; Nabavi et al., 2015; Peng and Jiang, 2015) Anxiety disorders, including GAD, phobias as well as PD, PTSD and OCD may have a significant impact on the onset, clinical phenomenol- ogy and prognosis of major affective disorders (MAFD). For example, ⁎ Correspondence to: IMPACT Strategic Research Center, Barwon Health, Deakin University, Geelong, Vic, Australia. Email address: dr.michaelmaes@hotmail.com (M. Maes) URL: http://scholar.google.co.th/citations?user=1wzMZ7UAAAAJ&hl=th&oi=ao https://doi.org/10.1016/j.psychres.2017.11.024 Received 28 June 2017; Received in revised form 25 October 2017; Accepted 6 November 2017 Available online xxx 0165-1781/ © 2017.