Negative experiences in childhood and the development and course of bipolar disorder

The aim of this paper is to review the effects of negative childhood experiences on the development and course of bipolar disorder (BD) and to discuss the involved mechanisms. The negative childhood experiences that may play a role in BD are critical or traumatic events including all kinds of abuse, loss of a parent or parents resulting from death, suicide, separation, divorce or prolonged separation. Previous studies indicate that in BD patients negative childhood events are more frequent than in control group. In BD patients these events are associated with an earlier onset and more severe course of the illness, including more frequent relapses, suicidal behavior, substance abuse and somatic diseases. This paper presents the possibility of the specific impact of individual events on the clinical outcome of BD. Mechanisms explaining the impact of negative childhood events on the development and course of BD include the interaction between biological predisposition and stress factors, the concept of kindling and activation of negative cognitive schemas. Early negative experiences cause a modification of the expression of the mediators of stress and neurotransmitters in certain areas of the brain. The interaction of these mediators with the development of neural networks may lead to longlasting structural and functional changes. Molecular genetic studies indicate the possibility of interactions between environmental factors (stress) and the polymorphisms of serotonin transporter, brain-derived neurotrophic factor (BDNF) and toll-like receptor (TLR2). It has also been hypothesized that childhood experiences affect DNA methylation, acting as a form of molecular memory and modifying brain activity over the next decade.