Biomarkers in bipolar disorder : a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force

Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.

Emotional invalidation and borderline personality disorder: a test of theory

Borderline Personality Disorder is a severe and debilitating mental health condition. The research conducted for this thesis demonstrated how invalidation in past and current meaningful relationships is associated with symptoms of the disorder in adulthood, and thereby advances our understanding of the disorder’s aetiology and targets for treatment.

Diet and sleep in children with attention deficit hyperactivity disorder : Preliminary data in Australian children

Sleep disturbances are common and consequential in children with attention deficit hyperactivity disorder (ADHD). Diet also influences ADHD symptoms. Interrelationships between diet, sleep and behaviour in children diagnosed with ADHD are little studied. We investigated, via parental report, the relationships between sleep and diet in 88 Australian children aged 6—13 years old (M = 8.94, SD = 1.78). This pilot data shows that 30 per cent of the children had sleep disturbance (≥ 2 standard deviations above the mean) with significant relationships between ADHD symptoms, sleep disturbance and diet. Parents who reported more sleep disturbance also reported a higher intake of carbohydrate, fats, and, most particularly, sugar which was also a significant predictor of night time sweating. These findings suggest an interrelationship between diet and sleep in children with ADHD. Given that both sleep and dietary intake are potentially modifiable behaviours within treatment regimes of children with ADHD, further investigation is needed.

Treatment response for acute depression is not associated with number of previous episodes: lack of evidence for a clinical staging model for major depressive disorder

Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness.

Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled.

There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.

We do not see things as they are, we see them as we are : a multidimensional worldview model of obsessive-compulsive disorder

Cognitive-behavioral models of obsessive-compulsive disorder (OCD) assign a central role to specific beliefs and coping strategies in the development, maintenance and exacerbation of obsessive-compulsive (OC) symptoms. These models also implicate perceptions of self and the world in the development and maintenance of OC phenomena (e.g., overestimation of threat, sociotropy, ambivalent or sensitive sense of self, looming vulnerability), although such self and world domains have not always been emphasized in recent research. Following recent recommendations (Doron & Kyrios, 2005), the present study undertook a multifaceted investigation of self and world perceptions in a nonclinical sample, using a coherent worldview framework (Janoff-Bulman, 1989, 1991). Beliefs regarding the self and the world were found to predict OC symptom severity over and above beliefs outlined in traditional cognitive-behavioral models of OCD. Self and world beliefs were also related to other OC-relevant beliefs. Implications of these findings for theory and treatment of OCD are discussed.

Cognitive behavioral treatment of obsessive compulsive disorder : a broader framework

Obsessive Compulsive Disorder (OCD) is rated as a leading cause of disability by the World Health Organization (1996). OCD is a heterogeneous and complex anxiety disorder characterized by the occurrence of repeated and distressing intrusive thoughts, and compulsive actions that are performed in order to lessen distress or prevent the negative outcome associated with the intrusions. Over the last several decades, cognitive behavioral treatments (CBT) of OCD have dramatically improved the prognosis for the disorder. However, a significant proportion of individuals presenting with OCD may still fail to benefit from treatment. In this paper, we present current CBT treatment models of OCD. We then propose several ways of enhancing CBT for OCD by targeting clients' attachment anxiety and dysfunctional self perceptions.