Neurohormonal Modulation of Memory

Hormones released during stress, including catecholamines and cortisol, modulate the encoding and retrieval of memory (McGaugh, 2000).

Administration of epinephrine (which is released from the adrenal) affects memory retention with an inverted U-shaped curve. Memory improves up to a point and decreases with high doses (Gold & van Buskirk, 1975; Liang, Juler, & McGaugh, 1986). Lower doses of norepinephrine injected into the amygdala promote memory for an inhibitory-avoidance task, while higher doses inhibit memory (Liang, McGaugh, & Yao, 1990). In humans, noradrenergic beta-blocker medications blocked the formation of emotional memories (Cahill, Prins, Weber, & McGaugh, 1994), while enhanced norepinephrine release was associated with enhanced encoding of emotional memories (Southwick et al., 2002). Vasopressin and oxy-tocin have been shown to modulate memory formation in both animals (McGaugh, 2000) and human subjects (including those with PTSD) (Pitman, Orr, & Lasko, 1993).

Glucocorticoids also affect learning and memory. Elevations of glu-cocorticoids within the physiological range result in reversible deficits in memory function in animals (Bodnoff et al., 1995; Oitzl & de Kloet, 1992) as well as human subjects (de Quervain, Roozendaal, Nitsch, Mc-Gaugh, & Hock, 2000; Kirschbaum, Wolf, May, Wippich, & Hellhammer, 1996; Lupien, Gillin, & Hauger, 1999; Lupien et al., 1997; Lupien et al., 2002; Newcomer, Craft, Hershey, Askins, & Bardgett, 1994; Newcomer et al., 1999; Wolf, Schommer, Hellhammer, McEwen, & Kirschbaum, 2001). Glucocorticoids released during stress, possibly acting through the hippocampus, may explain in part the acutely reversible as well as chronic effects that stress has on declarative memory (de Kloet et al., 1999; Kirschbaum et al., 1996; Porter & Landfield, 1998; Wolf, 2003). Greater deficits are seen in younger subjects in comparison to older subjects, hypothesized to be secondary to age-related decreases in glucocor-ticoid receptor density (Newcomer, Selke, Kelly, Paras, & Craft, 1995). Impairment of working memory by glucocorticoids may require nor-adrenergic stimulation to have its effect (Elzinga & Roelofs, 2005). We used a protocol of 1 mg of dexamethasone, followed by 2 mg one day later, and found an impairment in declarative memory function (percent retention of a paragraph after a delay) in healthy subjects but not in patients with depression (Bremner, Vythilingam, Vermetten, Newcomer, & Charney, 2004) or PTSD (Bremner et al., 2005b). We hypothesized that this might be due to disease-related decreases in glucocorticoid receptor function. This is consistent with the idea of PTSD as an "accelerated aging" (Bremner & Narayan, 1998) related to common theories of progressive hippocampal atrophy and dysfunction in both processes. We have also shown that endogenous cortisol release stimulated by a cognitive stress challenge in healthy subjects impaired delayed recall of words and a spatial memory task (Elzinga, Bakker, & Bremner, 2005). Some studies have shown, however, that endogenous cortisol levels in healthy subjects who became upset during a social speech task were correlated with enhanced delayed memory recall of unpleasant pictures (Abercrom-bie, Speck, & Monticelli, 2005). These discrepant findings may be related to different effects of endogenous cortisol on recall of verbal versus visual materials.

Stress-related release of neurohormones can influence recall of childhood abuse memories. As noted above, the stress hormones catechol-amines and cortisol influence the encoding and retrieval of memory. These neurohormones can be released at varying levels at the time of stress, thus influencing the encoding of traumatic memory. Also, they can be released at varying concentrations in an unpredictable manner at the time of memory retrieval. In addition, as reviewed above, release of these stress hormones is altered in patients with stress-induced mental disorders, which may lead to different outcomes than in healthy subjects.

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