Vulnerability to depression is associated with a failure to acquire implicit social appraisals.

Major depressive disorder (MDD) is associated with disrupted relationships with partners, family, and peers. These problems can precipitate the onset of clinical illness, influence severity and the prospects for recovery. Here, we investigated whether individuals who have recovered from depression use interpersonal signals to form favourable appraisals of others as social partners. Twenty recovered-depressed adults (with >1 adult episode of MDD but euthymic and medication-free for six months) and 23 healthy, never-depressed adults completed a task in which the gaze direction of some faces reliably cued the location a target (valid faces), whereas other faces cued the opposite location (invalid faces). No participants reported awareness of this contingency, and both groups were significantly faster to categorise targets following valid compared with invalid gaze cueing faces. Following this task, participants judged the trustworthiness of the faces. Whereas the healthy never-depressed participants judged the valid faces to be significantly more trustworthy than the invalid faces; this implicit social appraisal was absent in the recovered-depressed participants. Individuals who have recovered from MDD are able to respond appropriately to joint attention with other people but appear to not use joint attention to form implicit trust appraisals of others as potential social partners.

Preliminary evidence that sub-chronic citalopram triggers the re-evaluation of value in intimate partnerships.

Depression frequently involves disrupted inter-personal relationships, while treatment with serotonergic anti-depressants can interfere with libido and sexual function. However, little is known about how serotonin activity influences appraisals of intimate partnerships. Learning more could help to specify how serotonergic mechanisms mediate social isolation in psychiatric illness. Forty-four healthy heterosexual adults, currently in romantic relationships, received 8 days treatment with the selective serotonin re-uptake inhibitor citalopram (N = 21; 10 male) or placebo (N = 23; 12 male). Participants viewed photographs of unknown, heterosexual couples and made a series of judgements about their relationships. Participants also indicated the importance of relationship features in their own close partnerships, and close partnerships generally. Citalopram reduced the rated quality of couples' physical relationships and the importance attributed to physical and intimate aspects of participants' own relationships. In contrast, citalopram also enhanced the evaluated worth of mutual trust in relationships. Amongst males, citalopram was associated with judgements of reduced turbulence and bickering in others' relationships, and increased male dominance. These data constitute preliminary evidence that enhancing serotonin activity modulates cognitions about sexual activity as part of a re-appraisal of sources of value within close intimate relationships, enhancing the judged importance of longer-term benefits of trust and shared experiences.

I want to help you, but I am not sure why: gaze-cuing induces altruistic giving.

Detecting subtle indicators of trustworthiness is highly adaptive for moving effectively amongst social partners. One powerful signal is gaze direction, which individuals can use to inform (or deceive) by looking toward (or away from) important objects or events in the environment. Here, across 5 experiments, we investigate whether implicit learning about gaze cues can influence subsequent economic transactions; we also examine some of the underlying mechanisms. In the 1st experiment, we demonstrate that people invest more money with individuals whose gaze information has previously been helpful, possibly reflecting enhanced trust appraisals. However, in 2 further experiments, we show that other mechanisms driving this behavior include obligations to fairness or (painful) altruism, since people also make more generous offers and allocations of money to individuals with reliable gaze cues in adapted 1-shot ultimatum games and 1-shot dictator games. In 2 final experiments, we show that the introduction of perceptual noise while following gaze can disrupt these effects, but only when the social partners are unfamiliar. Nonconscious detection of reliable gaze cues can prompt altruism toward others, probably reflecting the interplay of systems that encode identity and control gaze-evoked attention, integrating the reinforcement value of gaze cues.

Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype.

Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals at-risk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects ('feel high': F=14.2, p=0.001; 'feel effects': F=8.1, p=0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

Serotonergic activity influences the cognitive appraisal of close intimate relationships in healthy adults.

BACKGROUND: Close supportive relationships protect against psychological disorders and also facilitate recovery. However, little is known about the neurochemical mechanisms that mediate these effects. Variation in serotonin function influences affiliative behavior in humans and nonhuman primates. Here, we used tryptophan depletion in healthy adults to investigate the role of serotonin in the cognitive appraisal of close personal relationships. METHODS: Twenty-two healthy adults drank an amino acid drink without tryptophan, and 19 healthy adults drank an amino acid drink containing tryptophan. Participants were presented with color photographs of heterosexual "couples" standing apart or making affiliative touch gestures and rated the couples for descriptors that capture qualities of close personal relationships. Trait attachment style and state affect of participants were also measured. RESULTS: Tryptophan depletion reduced the judged intimacy and romance of photographed couples. Tryptophan-depleted women rated men as more dominant in relationships and touching couples as more able to resolve their conflicts, when compared with nondepleted women. These effects were not due to changes in mood and remained statistically reliable when the marked impact of attachment style upon relationship judgments was statistically controlled. CONCLUSIONS: Our results suggest that central serotonin activity influences the appraisal of close intimate partnerships, raising the possibility that serotonergic dysfunction contributes to altered cognitions about relationships in psychiatric illnesses.

Serotonin and dopamine play complementary roles in gambling to recover losses.

Continued gambling to recover losses--'loss chasing'--is a prominent feature of social and pathological gambling. However, little is known about the neuromodulators that influence this behavior. In three separate experiments, we investigated the role of serotonin activity, D(2)/D(3) receptor activity, and beta-adrenoceptor activity on the loss chasing of age and IQ-matched healthy adults randomized to treatment or an appropriate control/placebo. In Experiment 1, participants consumed amino-acid drinks that did or did not contain the serotonin precursor, tryptophan. In Experiment 2, participants received a single 176 µg dose of the D(2)/D(3) receptor agonist, pramipexole, or placebo. In Experiment 3, participants received a single 80 mg dose of the beta-adrenoceptor blocker, propranolol, or placebo. Following treatment, participants completed a computerized loss-chasing game. Mood and heart rate were measured at baseline and following treatment. Tryptophan depletion significantly reduced the number of decisions made to chase losses, and the number of consecutive decisions to chase, in the absence of marked changes in mood. By contrast, pramipexole significantly increased the value of losses chased and diminished the value of losses surrendered. Propranolol markedly reduced heart rate, but produced no significant changes in loss-chasing behavior. Loss chasing can be thought of as an aversively motivated escape behavior controlled, in part, by the marginal value of continued gambling relative to the value of already accumulated losses. Serotonin and dopamine appear to play dissociable roles in the tendency of individuals to gamble to recover, or to seek to 'escape' from, previous losses. Serotonergic activity seems to promote the availability of loss chasing as a behavioral option, whereas D(2)/D(3) receptor activity produces complex changes in the value of losses judged worth chasing. Sympathetic arousal, at least as mediated by beta-adrenoceptors, does not play a major role in laboratory-based loss-chasing choices.

Altered risk-aversion and risk-seeking behavior in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is associated with high-risk behaviors, such as gambling and impulsivity. However, little is known about the psychological factors that influence these behaviors or their significance for the development of the disorder. In this study, we investigated the effects of highlighting rewards versus highlighting punishments in the risky decision-making of euthymic individuals with bipolar disorder. METHODS: Twenty euthymic, medication-free men and women with previously undiagnosed bipolar II or bipolar disorder not otherwise specified and 20 age- and IQ-matched healthy men and women completed a computerized risky decision-making task in which mathematically equivalent dilemmas were presented in terms of opportunities to gain rewards ("positively-framed") or to avoid suffering losses ("negatively-framed"). The dependent measures were the proportion of risk-seeking choices (and deliberation times) when making decisions in positively versus negatively framed dilemmas. RESULTS: As expected, healthy control participants made more risky-seeking choices in response to the negatively framed dilemmas compared with the positively framed dilemmas. However, this effect was significantly attenuated in BD participants who also took significantly longer to make risk-averse responses to the positively framed dilemmas. The BD participants overestimated the number of bad outcomes arising out of positively framed dilemmas. CONCLUSIONS: These data demonstrate that risky choice in BD is associated with reduced sensitivity to emotional contexts that highlight rewards or punishments, possibly reflecting altered valuations of prospective gains and losses associated with behavioral options.

The effects of low doses of delta-9 tetrahydrocannabinol on reinforcement processing in the risky decision-making of young healthy adults.

Research suggests that risky decision-making is sensitive to neuromodulatory influences acting upon corticolimbic circuitry. However, while other evidence attests to effects of delta-9 tetrahydrocannabinol (THC) on the activity of reward pathways, relatively little is known about the possible involvement of cannabinoid activity in risky choice. In this experiment, we examined the effects of a single sublingual 5 mg dose of THC on a test of risky decision-making (requiring choices between simultaneously presented gambles differing in their magnitude of gains, magnitude of losses and the probability with which these outcomes were delivered). Tests of non-normative decision-making involving risk-aversion when deciding between gains and risk-seeking choices when deciding between losses were also included. In all, 15 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, cross-over design. THC had three principal effects relative to placebo: (i) THC reduced choice of gambles with variable gains and losses, but increased choice of gambles with zero-expected value; (ii) THC reduced participants' attention towards losses when the probability of winning was low (and the probability of losing was high); and (iii) THC speeded participants' responses to gambles with large compared to small potential gains. These results suggest that THC mediates specific motivational processes and the processing of reinforcement cues during risky choice, perhaps reflecting altered CB1 receptor or catecholamine activity within corticolimbic pathways.

Low doses of delta-9 tetrahydrocannabinol (THC) have divergent effects on short-term spatial memory in young, healthy adults.

Evidence suggests that manipulating spatial information within working memory depends upon a circuitry organized around the prefrontal cortex (PFC) and the activity of the catecholamine systems. Other evidence attests to the effects of Delta-9 tetrahydrocannabinol (THC) on short-term spatial memory function, most probably involving CB(1) receptor activity within hippocampal circuitries. At the current time, there have been no systematic studies of the effects of THC on spatial working memory in human subjects using tasks known to depend upon frontotemporal neural circuitries. We examined the effects of a single sublingual 5 mg dose of THC on a test of spatial working memory (requiring active manipulation of remembered spatial information for the management of future behavior) and a test of spatial span (requiring only the reproduction of sequences of previously presented spatial cues). In all, 19 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, crossover design. Male participants performed more accurately than female participants. THC significantly enhanced spatial working memory performance of female participants. By contrast, male and female participants produced more intrusion errors during performance of the Spatial Span task. These results suggest that THC has relatively complex effects on spatial memory in human subjects, perhaps reflecting altered CB(1) receptor activity within frontotemporal circuits or altered activity of mesocortical dopaminergic pathways in PFC areas associated with spatial memory.