Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports

Diphenhydramine is a widely used antihistaminic that is frequently included in over-the-counter medications. Due to its sedating properties, diphenhydramine is used in some hypnotic preparations. Occasionally, patients respond to diphenhydramine with paradoxical excitation. There are no studies on the prevalence of paradoxical excitation in healthy subjects. Diphenhydramine appears to cause mild inhibition of the cytochrome P450 (CYP) 2D6 enzyme. This can be interpreted as competitive inhibition, suggesting that diphenhydramine may be a CYP2D6 substrate. When subjects have at least three active copies of the CYP2D6 gene, they are called ultrarapid metabolizers (UMs) and present high metabolic capacity for CYP2D6 substrates. In the United States, CYP2D6 UMs may account for approximately 1% to 2% of the population. We describe three CYP2D6 UMs who reported paradoxical excitation on diphenhydramine. These cases suggest that in CYP2D6 UMs, diphenhydramine may be converted to a compound that causes excitation due to the abnormally high CYP2D6 activity. Therefore, such individuals may be at higher risk for excitation. Although these are only three anecdotal cases of paradoxical excitation from three CYP2D6 UMs, the reports illustrate the need for larger, more formal studies of diphenhydramine responses in CYP2D6 UMs and of diphenhydramine metabolism.     

Perceptual Indiscriminability: In Defence of Wright's Proof

A series of unnoticeably small changes in an observable property may add up to a noticeable change. Crispin Wright has used this fact to prove that perceptual indiscriminability is a non-transitive relation. Delia Graff has recently argued that there is a 'tension' between Wright's assumptions. But Graff has misunderstood one of these, that 'phenomenal continua' are possible; and the other, that our powers of discrimination are finite, is sound. If the first assumption is properly understood, it is not in tension with but is actually implied by the second, given a plausible physical assumption.     

Foster Care Children’s Kinship Involvement and Behavioral Risks: A Longitudinal Study

Researchers have found that individual strengths (e.g., coping, optimism) are protective against behavioral risk (e.g., delinquency, suicide) among traumatized youth in foster care. However, less is known about kinship involvement (i.e., extended family support) as a social strength that can also attenuate the effects of childhood trauma, thereby reducing behavioral risk. Addressing the lack of research on kinship involvement, the present longitudinal study investigated individual strengths (IS) and kinship involvement (KI) as moderators between trauma experiences (TE) and risk behaviors (RB) among 336 youth, ages 6 to 13, who entered the Illinois child welfare system between 2011 and 2014. Controlling for Time 1 (T1) RB, T1 IS, age, gender, and ethnicity, we utilized a three-level Hierarchical Generalized Linear Model to analyze TE?×?KI and TE?×?IS at T2. The study found that KI was negatively associated with RB (β16?=??.08, Event Rate Ratio [ERR]?=?0.92, p?=?<.01), suggesting that youth with more KI had relatively lower RB trajectories. Further, the TE?×?IS interaction was significant in the model (β21?=??.05, ERR?=?0.95, p?<?.01); TE was positively associated with RB at lower levels of IS but not higher levels of IS. These results highlight the importance of assessing children’s kinship networks and individual strengths early in foster care.     

Logic,Rules and Intention: The Principal Aim Argument

Stephen Mumford develops his view of sport spectatorship partly through a rejection of an argument he attributes to Best, which distinguishes between two categories of sports, the ‘purposive’ and the ‘aesthetic’, on the basis of the claim that they have different principal aims. This paper considers the principal aim argument and one feature of Mumford’s rejection of that argument, namely, Best’s observation that the distinctions to which he draws attention are based on logical differences. The paper argues that Mumford misconstrues Best’s argument by taking it to be about the intentions of players and athletes, while it is actually about a specific feature of the rules of each sport.     

Reason and Coercion: In defence of a Rational Control Account of Freedom

According to Pettit, an account of freedom in terms of rational control fails to suffice, for he argues that such an account lacks the resources to rule out coerced actions as unfree. The crucial feature of a coerced action is that it leaves the agent with a choice to make, an apparently rational choice to make. To the extent that it does this, it would seem to leave the agent as free as he would be in any other case where there is a choice to be made. However, we do not consider actions that are coerced to be on a par with actions that are not coerced, that are performed freely as we might say. We do not hold agents similarly responsible in the two sorts of cases. So it would seem that the rational control account fails, for it appears to fail to vindicate this differential practice. In this paper, I defend the rational control account. I outline two ways in which proponents of a rational control model, broadly understood, can respond to this criticism.     

Attentional bias in high- and low-anxious individuals: evidence for threat-induced effects on engagement and disengagement

Attentional bias to threatening visual stimuli (words or pictures) is commonly present in anxious individuals, but not in non-anxious people. There is evidence to show that attentional bias to threat can be induced in all individuals when threat is imposed by threat not of symbolic nature, but by cues that predict aversive stimulation (loud noise or electric shock). However, it is not known whether attentional bias in such situations is still influenced by individual differences in anxiety. This question was addressed in two experiments using a spatial cuing task in which visual cues predicted the occurrence of an aversive event consisting of a loud human scream. Speeded attentional engagement to threat cues was positively correlated with trait anxiety in Experiment 1. Experiment 2 showed that speeded attentional engagement was present only in participants selected for high anxiety but not in low-anxious participants. In both experiments, slower disengagement from threat cues was found in all participants, irrespective of their trait anxiety levels.     

Exchange schedules in token economies: A preliminary investigation of second‐order schedule effects

Basic research shows that token‐production and exchange‐production schedules in token economies affect each other as second‐order schedules (i.e., the exchange‐production schedule's requirements affect responding toward the token‐production schedule). This relationship has not been investigated with children in academic settings despite the widespread use of token economies in this context. This study compared the effects of fixed‐ratio (FR) and variable‐ratio (VR) exchange‐production schedules of equal ratios (2, 5, and 10) on responding toward an FR 1 token‐production schedule with a child diagnosed with autism. A concurrent chains assessment was also conducted to assess the participant's relative preference for FR and VR exchange‐production schedule arrangements within her typical discrete trial training. Results showed no difference in response rate between the two schedule types. However, the concurrent chains assessment revealed an exclusive preference for the VR arrangement.     

Affective aprosodia from a medial frontal stroke

BACKGROUND AND OBJECTIVES: Whereas injury to the left hemisphere induces aphasia, injury to the right hemisphere's perisylvian region induces an impairment of emotional speech prosody (affective aprosodia). Left-sided medial frontal lesions are associated with reduced verbal fluency with relatively intact comprehension and repetition (transcortical motor aphasia), but persistent affective prosodic defects associated with right medial frontal lesions have not been described. METHODS: We assessed the prosody of a man who sustained a right medial frontal cerebral infarction seven years prior. RESULTS: While propositional speech expression was normal including syntactic prosody, the patient was impaired at expressing emotions using prosody. His comprehension and repetition of prosody were also impaired but less so than expression. CONCLUSIONS: Right medial frontal lesions can induce an affective aprosodia that primarily impairs expression.     

The treatment of sexual dysfunction: Some theoretical considerations

Journal of Contemporary Psychotherapy -