ABSTRACT
An emerging hypothesis suggests that the pathogenesis of suicidal behavior and depression involves altered neural plasticity (Garcia, 2002), resulting in the inability of the brain to make appropriate adaptive responses to environmental stimuli (Duman et al., 2000; Fossati et al., 2004). This hypothesis is supported by studies showing altered brain structure during stress and in depressed and suicidal patients. These alterations include a reduction in cell number, density, cell body size, and neuronal and glial density in frontal cortical or hippocampal brain areas and a decrease in parahippocampal cortex cortical/laminar thickness (Altshuler et al., 1990; Rajkowska, 1997, 2000, 2002; Ongur et al., 1998; Rosoklija et al., 2000; Cotter et al., 2001, 2002; Miguel-Hidalgo and Rajkowska, 2002). In addition, changes in synaptic circuitry (Aganova and Uranova, 1992), decreased dorsolateral prefrontal cortical (PFC) activity (Dolan et al., 1993; Drevets et al., 1998), impaired synaptic connectivity between the frontal lobe and other brain regions (Andreasen, 1997; Honer, 1999), changes in the number and shape of dendritic spines (Toni et al., 1999; Hajsza et al., 2005), changes in the primary location of synapse formation, altered dendritic morphological characteristics of neurons in the hippocampus, a decrease in length and number of apical dendrites (McEwen, 2000), neuronal atrophy and
8.1 Introduction .................................................................................................. 139 8.2 Stress and BDNF .......................................................................................... 141 8.3 BDNF and Suicide ........................................................................................ 144
8.3.1 Human Postmortem Brain Studies ................................................... 144 8.3.2 Genetic Linkage Studies ................................................................... 145 8.3.3 BDNF Studies in Suicidal Patients and Comparison of Suicidal
and Nonsuicidal Depressed Patients ................................................. 147 8.4 BDNF Receptors in Suicidal Behavior ......................................................... 148 8.5 Conclusion and Future Studies ..................................................................... 151 Acknowledgments .................................................................................................. 152 References .............................................................................................................. 152
a decreased volume of the hippocampus (Sheline, 2000; Sala et al., 2004; Frodl et al., 2006), a decreased number of neurons and glia in cortical areas (Rajkowska and Miguel-Hidalgo, 2007), and spatial cognition de”cits (Sackeim, 2001) have also been reported during stress and depression. Furthermore, stress, a major factor in suicide, hinders performance on hippocampal-dependent memory tasks and impairs induction of hippocampal long-term potentiation. These studies clearly demonstrate impaired structural and functional plasticity in depression and suicide.
