Review ArticlesKindling and second messengers: an approach to the neurobiology of recurrence in bipolar disorder
Section snippets
The kindling hypothesis
The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. As advanced by Post and his associates (Post and Weiss 1997), this theory builds on the physiological finding that intermittent subthreshold electrical or chemical stimuli produce increasingly strong neuronal depolarization in the brain, a process of sensitization that may possess temporal similarities to the episodic behavioral disturbances of bipolar
Signal transduction and kindling: is there a connection?
Second-messenger systems have been implicated in amygdaloid kindling and stimulant-induced behavioral and biochemical sensitization. Much of this work has been conducted by Kalivas and colleagues, who have demonstrated G-protein mediated effects in cocaine-sensitized animals. For instance, in one study, rats who had been behaviorally sensitized to cocaine preferentially showed a reduction in G-protein adenosine diphosphate ribosylation in the ventral tegmental area with in vitro pertussis toxin
Research on second-messenger systems
The kindling hypothesis dovetails with neurobiological research which demonstrates that stress can activate a cascade of changes in the brain that play out over progressively longer time frames. In animal studies of kindling, Post and associates (Post et al 1995) have reported changes in genetic expression (of c-fos and thyroid-releasing hormone genes) as a result of repeated intermittent electrical and chemical stimulation. These genetic changes are mediated by intermediary processes: the
Conclusions
In animal studies of kindling, it has been demonstrated that changes in the neural substrate can be elicited by repeated intermittent stimulation. In animal and human studies of lithium, and in patients with bipolar disorder, changes in G-proteins, PI, PKC, MARCKS, and calcium activity have been described, along with changes in c-fos expression. Along with the growing empirical evidence supporting kindlinglike phenomena in clinical studies of bipolar disorder, these lines of research appear to
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2015, Clinical Psychology ReviewCitation Excerpt :A more detailed consideration of anxiety and its treatment within BPSD is clearly warranted. Psychosocial stressors are implicated in the onset of BPSD episodes (Ghaemi, Boiman, & Goodwin, 1999) and psychosocial interventions are increasingly emphasised in clinical guidance (Goodwin, 2003; Hirschfeld et al., 2004; National Institute for Health & Clinical Excellence [NICE], 2014). The need for close integration between psychological/psychosocial and pharmacological approaches, with psychological intervention adjunctive to long-term maintenance pharmacotherapy, is now well recognised (Goodwin & Consensus Group of the British Association for Psychopharmacology, 2009).
Is there an association between suicide attempt and delay of initiation of mood stabilizers in bipolar i disorder?
2012, Journal of Affective DisordersCitation Excerpt :This finding supports the possibility that anticonvulsant mood stabilizers offer similar protective benefits against non-lethal suicide behavior as lithium. Specifically in bipolar disorder, current theories about episode recurrence and long-term morbidity suggest that poorer treatment outcome may be in part from behavior sensitization or kindling-like mechanisms due to frequent uncontrolled episodes (Ghaemi et al., 1999). A recent study shows that individuals at the earliest stages of illness consistently had a more favorable response to treatment (Berk et al., 2011).
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2012, Handbook of Clinical NeurologyCitation Excerpt :These findings may explain functional impairments seen in depression. SCN abnormalities may also alter “free-running” rhythms, cycles that are not entrained to the 24-hour day/night cycle, which may desynchronize other circadian rhythms, adversely affecting mood (Ghaemi et al., 1999). This hypothesis has been recently supported by an animal model of a genetically fast biological clock in rats missing the tau gene, with behavioral characteristics roughly analogous to manic-depressive symptoms (Lowrey et al., 2000).
Life stress and kindling in bipolar disorder: Review of the evidence and integration with emerging biopsychosocial theories
2011, Clinical Psychology ReviewCitation Excerpt :A final methodological challenge is more specific to BD. As compared to other psychological disorders, the initial onset of BD can be more difficult to pinpoint chronologically (Ghaemi et al., 1999). Those with BD often experience depressive episode(s) prior to their first (hypo)manic episode, and in these cases, a BD diagnosis would not be immediately evident.
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