RECURRENT AFFECTIVE-DISORDER - ROOTS IN DEVELOPMENTAL NEUROBIOLOGY AND ILLNESS PROGRESSION BASED ON CHANGES IN GENE-EXPRESSION

Electrophysiological kindling and behavioral sensitization to psychomo tor stimulants and stress provide paradigms for understanding how repe ated acute events can leave neurobiological residues in gene expressio n, accounting for the observed long-lasting alterations in behavioral responsivity. Kindling helps conceptualize how repeated electrical sti mulation of the brain can progressively evoke increased behavioral and convulsive responsivity, leading to spontaneous seizures in the absen ce of exogenous stimulation following sufficient stimulations. As kind ling unfolds, a complex spatiotemporal cascade of events occurs and in cludes the induction of immediate early genes (e.g., c-fos) and late e ffector genes (including peptides and growth factors) possible associa ted with the observed changes in brain microstructure (e.g., synapse f ormation, axonal and dendritic sprouting, apoptosis). Behavioral sensi tization to psychomotor stimulants and stress has also been shown to i nduce related but different cascades of effects on immediate early and late effector gene expression. These may be associated with the obser bed long-lasting alterations in behavioral responsivity based on prior experience. If these types of alterations are put into a developmenta l context, this would provide a paradigm for understanding how early l ife events could exert profound and behaviorally relevant biochemical and microstructural effects on the central nervous system of the devel oping organism. The conceptual overview offered by the sensitization a nd kindling models suggests that environmentally triggered neurobiolog ical processes do not form a single or static residue but, instead, en gage processes related to developmental neurobiology and learning and memory and whose substrate is constantly evolving over an organism's l ifetime.