Differential Behavioral Effects of Plasma Tryptophan Depletion and Loading in Aggressive and Nonaggressive Men

Abstract

Preliminary findings indicate that men with high trait hostility may be prone to aggression increases following plasma tryptophan (Trp) depletion. We measured laboratory aggression in men selected for presence (n ϭ12Substantial research has implicated decreased serotonin (5-HT) neurotransmission in human aggressive behavior (Brown et al. 1979;Coccaro et al. 1997a;Linnoila et al. 1983;Virkkunen et al. 1994). In recent neuroendocrine challenge studies, aggression has correlated negatively with plasma prolactin (PRL) elevations following the administration of the 5-HT agonist fenfluramine (Coccaro et al. 1996;Manuck et al. 1998). In another recent report, PRL responses to both fenfluramine and m -CPP were blunted in personality-disordered individuals with high self-reported hostility (Coccaro et al. 1997a). Finally, other physiological responses to serotonergic agonists fenfluramine (Coccaro et al. 1996) and ipsapirone (Moeller et al. 1998) were inversely correlated with rates of laboratory aggression.While these correlational data are compelling, the strongest support for the hypothesis that dysfunctional 5-HT neurotransmission facilitates aggression is prospectively-measured behavior change after the impairment or enhancement of the 5-HT system. This research in humans can be difficult in that serotonin-specific drugs can take days to weeks to exert any mood and/or behavior effects, and these effects may be too subtle for detection by many laboratory measures. Nevertheless, some data have shown a tendency for serotonergic drugs to decrease aggression in humans. For example, From NO . 4 fluoxetine (Coccaro et al. 1997c) and sertraline (Kavoussi et al. 1994) attenuated clinician-rated impulsive aggression in psychiatric patients. Heiligenstein et al. (1993) meta-analyzed data from thousands of patients in several clinical trials of fluoxetine and found that aggressive acts were reported in only 0.15% of fluoxetinetreated patients, but 0.65% of placebo-treated patients. When aggression was measured prospectively, fluoxetine was effective in decreasing aggression in a psychiatric outpatients selected for prominent impulsive aggression (Coccaro and Kavoussi 1997).The administration of a beverage of large neutral amino acids (LNAAs) which lacks 5-HT precursor L-tryptophan (Trp) can rapidly alter brain 5-HT (Young et al. 1985). This technique, called "tryptophan depletion," reduces brain Trp uptake in two ways: 1) LNAAs competitively inhibit active transport of Trp across the blood-brain barrier (Yuwiler et al. 1977), and 2) endogenous plasma Trp is incorporated into proteins in the hepatic response to the LNAA load (Gessa et al. 1975). Animal research has shown that Trp depletion dosedependently reduces brain levels of Trp, 5-HT, and the 5-HT metabolite 5-HIAA within a few hours (Biggio et al. 1974;Moja et al. 1989).In humans, Trp depletion has decreased synthesis rates of a 5-HT analogue in the brain in a PET scanning experiment (Nishizawa et al. 1997), and has reduced cerebrospinal fluid concentrations of 5-HIA...

Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

“…It is consistent with other work showing that ATD affects impulsive behavior only in certain individuals (Cherek and Lane, 1999;LeMarquand et al, 1999;Bjork et al, 2000;Marsh et al, 2002;Swann et al, 2002; but see Crean et al, 2002).…”

“…CSF concentrations of the 5-HT metabolite 5-HIAA correlate inversely with impulsive behaviors in many neuropsychiatric and personality disorders including aggressive, conduct, and attention-deficit/hyperactivity disorders (Evenden, 1999). Furthermore, recent studies with human volunteers have found that ATD increases impulsive and aggressive behavior, although these effects appear to depend on individual differences in impulsive personality traits (Cherek and Lane, 1999;LeMarquand et al, 1999;Dougherty et al, 1999;Bjork et al, 2000;Marsh et al, 2002;Crean et al, 2002). Findings from studies with clinical human populations are corroborated by an extensive number of animal studies, which suggest that impulsive choice in delaydiscounting paradigms and premature responding in choice reaction-time tasks implicate changes in the 5-HT system (Wogar et al, 1993;Harrison et al, 1997a, b;Puumala and Sirvio, 1998;Koskinen et al, 2000;Mobini et al, 2000;Dalley et al, 2002;Passetti et al, 2003;Winstanley et al, 2003;Liu et al, 2004).…”

Laboratory-Measured Aggressive Behavior of Women Acute Tryptophan Depletion and Augmentation

“…Other studies using normal males have reported conflicting results under Trp depletion (Bjork et al 1999;Moeller et al 1996;Pihl et al 1995;Smith et al 1986); for example, high-trait aggressive men have shown increases in both subjective paperand-pencil measures and in laboratory-measured behavioral aggression under Trp depletion, whereas lowtrait aggressive men have not (Cleare and Bond 1995). In our most recent laboratory studies (Bjork et al 1999(Bjork et al , 2000, Trp depletion increased aggressive behavior in men with high baseline levels of aggression but did not affect men with low baseline levels.Most studies of the relationship between CNS 5-HT function and aggressive/impulsive behaviors have relied on men. In our laboratory, we are conducting a series of systematic analyses of aggressive/impulsive behavior of women using a paradigm (PSAP, see below) to prospectively measure changes in aggressive responding as a result of experimental manipulation.…”

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

“…This indirectly supports the lack of effect of serotonin in the control of stopping because there are links between serotonin and some, although not all, forms of aggression. For example, serotonin depletion using ATD may increase aggression in subjective assessment and in laboratory tests such as the Point Subtraction Aggression Paradigm and Taylor Competitive Reaction Time Task (Bjork et al 1999(Bjork et al , 2000Cleare and Bond 1995;Moeller et al 1996;Pihl et al 1995;Salomon et al 1994).…”