Social-economical decision making in current and remitted major depression.

BACKGROUND: Prosocial emotions related to self-blame are important in guiding human altruistic decisions. These emotions are elevated in major depressive disorder (MDD), such that MDD has been associated with guilt-driven pathological hyper-altruism. However, the impact of such emotional impairments in MDD on different types of social decision-making is unknown. METHOD: In order to address this issue, we investigated different kinds of altruistic behaviour (interpersonal cooperation and fund allocation, altruistic punishment and charitable donation) in 33 healthy subjects, 35 patients in full remission (unmedicated) and 24 currently depressed patients (11 on medication) using behavioural-economical paradigms. RESULTS: We show a significant main effect of clinical status on altruistic decisions (p = 0.04) and a significant interaction between clinical status and type of altruistic decisions (p = 0.03). More specifically, symptomatic patients defected significantly more in the Prisoner's Dilemma game (p < 0.05) and made significantly lower charitable donations, whether or not these incurred a personal cost (p < 0.05 and p < 0.01, respectively). Currently depressed patients also reported significantly higher guilt elicited by receiving unfair financial offers in the Ultimatum Game (p < 0.05). CONCLUSIONS: Currently depressed individuals were less altruistic in both a charitable donation and an interpersonal cooperation task. Taken together, our results challenge the guilt-driven pathological hyper-altruism hypothesis in depression. There were also differences in both current and remitted patients in the relationship between altruistic behaviour and pathological self-blaming, suggesting an important role for these emotions in moral and social decision-making abnormalities in depression.

Temporal discounting in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with abnormalities in financial reward processing. Previous research suggests that patients with MDD show reduced sensitivity to frequency of financial rewards. However, there is a lack of conclusive evidence from studies investigating the evaluation of financial rewards over time, an important aspect of reward processing that influences the way people plan long-term investments. Beck's cognitive model posits that patients with MDD hold a negative view of the future that may influence the amount of resources patients are willing to invest into their future selves. METHOD: We administered a delay discounting task to 82 participants: 29 healthy controls, 29 unmedicated participants with fully remitted MDD (rMDD) and 24 participants with current MDD (11 on medication). RESULTS: Patients with current MDD, relative to remitted patients and healthy subjects, discounted large-sized future rewards at a significantly higher rate and were insensitive to changes in reward size from medium to large. There was a main effect of clinical group on discounting rates for large-sized rewards, and discounting rates for large-sized rewards correlated with severity of depressive symptoms, particularly hopelessness. CONCLUSIONS: Higher discounting of delayed rewards in MDD seems to be state dependent and may be a reflection of depressive symptoms, specifically hopelessness. Discounting distant rewards at a higher rate means that patients are more likely to choose immediate financial options. Such impairments related to long-term investment planning may be important for understanding value-based decision making in MDD, and contribute to ongoing functional impairment.

State-dependent changes in hippocampal grey matter in depression.

Reduced hippocampal volume has been reported in depression and may be involved in the aetiology of depressive symptoms and vulnerability to depressive relapse. Neuroplasticity following antidepressant drug treatment in the hippocampus has been demonstrated in animal models but adaptive changes after such treatment have not been shown in humans. In this study, we determined whether grey matter loss in the hippocampus in depression (1) is present in medication-free depressed (2) changes in response to antidepressant treatment and (3) is present as a stable trait in medication-free remitted patients. Sixty-four medication-free unipolar depressed patients: 39 currently depressed and 25 in remission, and 66 healthy controls (HC) underwent structural magnetic resonance imaging in a cross-sectional and longitudinal design. Thirty-two currently depressed participants were then treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring plasma citalopram concentration. We measured regional variation in grey matter concentration by using voxel-based morphometry-Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra. Patients with current depression had bilaterally reduced grey matter in the hippocampus compared with HC and untreated patients in stable remission with the latter groups not differing. An increase in grey matter was observed in the hippocampus following treatment with citalopram in currently depressed patients. Grey matter reduction in the hippocampus appears specific to the depressed state and is a potential biomarker for a depressive episode.

Attenuated responses to emotional expressions in women with generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD. METHOD: A total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner. RESULTS: The only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response. CONCLUSIONS: In contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes.

Interaction between a history of depression and rumination on neural response to emotional faces.

BACKGROUND: Both past depressive episodes and the personality trait of depressive rumination are strong risk factors for future depression. Depression is associated with abnormal emotional processing, which may be a neurobiological marker for vulnerability to depression. A consistent picture has yet to emerge as to how a history of depression and the tendency to ruminate influence emotional processing. The aim of this study was to investigate the relationship between rumination, past depression and neural responses when processing face emotions. METHOD: The Ruminative Responses Scale (RRS) was completed by 30 remitted depressives and 37 controls who underwent functional magnetic resonance imaging (fMRI) scanning while viewing happy, sad, fearful and neutral faces. RESULTS: The remitted depressives showed overall reductions in neural responses to negative emotions relative to the controls. However, in the remitted depressives, but not the controls, RRS scores were correlated with increased neural responses to negative emotions and decreased responses to happiness in limbic regions. CONCLUSIONS: Automatic emotion processing biases and rumination seem to be correlated to aspects of vulnerability to depression. However, remission from depression may be maintained by a general suppression of limbic responsiveness to negative emotion.

Transmission electron microscopy with a liquid flow cell.

The imaging of microscopic structures at nanometre-scale spatial resolution in a liquid environment is of interest for a wide range of studies. Recently, a liquid flow transmission electron microscopy (TEM) holder equipped with a microfluidic cell has been developed and shown to exhibit flow of nanoparticles through an electron transparent viewing window. Here we demonstrate the application of the flow cell system for both scanning and conventional transmission electron microscopy imaging of immobilized nanoparticles with a resolution of a few nanometres in liquid water of micrometre thickness. The spatial resolution of conventional TEM bright field imaging is shown to be limited by chromatic aberration due to multiple inelastic scattering in the water, and we demonstrate that the liquid in the cell can be displaced by a gas phase that forms under intense electron irradiation. Our data suggest that under appropriate conditions, TEM imaging with a liquid flow cell is a promising method for understanding the in situ behaviour of nanoscale structures in a prescribed and dynamically changing chemical environment.

Quantitative analysis of the effect of lesions of the subthalamic nucleus on intertemporal choice: further evidence for enhancement of the incentive value of food reinforcers.

Recent evidence suggests that the subthalamic nucleus (STN) is involved in regulating the incentive value of food reinforcers. The objective of this study was to examine the effect of lesions of the STN on intertemporal choice (choice between reinforcers differing in size and delay). Rats with bilateral quinolinic acid-induced lesions of the STN (n = 15) or sham lesions (n = 14) were trained in a discrete-trials progressive delay schedule to press levers A and B for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after a delay d(B). d(B) increased across blocks of trials; d(A) was manipulated across phases of the experiment. Indifference delay, d(B(50)) (value of d(B) corresponding to 50% choice of B), was estimated for each rat in each phase, and linear indifference functions (d(B(50)) vs. d(A)) were derived. The STN-lesioned group showed a flatter slope of the indifference function (implying higher instantaneous reinforcer values) than the sham-lesioned group; the intercepts did not differ between the groups. The results agree with recent evidence for a role of the STN in incentive value. Unlike some earlier studies, these results do not indicate a role of the STN in delay discounting.

Assessing human 5-HT function in vivo with pharmacoMRI.

A number of novel ways of using magnetic resonance imaging (MRI) to visualise the action of drugs on animal and human brain (pharmacoMRI or phMRI) are becoming established tools in translational psychopharmacology. Using drugs with known pharmacology it is possible to investigate how neurotransmitter systems are involved in neural systems engaged by other processes, such as cognitive challenge (modulation phMRI) or to examine the acute effects of the drug itself in the brain (challenge phMRI). In this article we discuss the principles behind phMRI and review studies investigating the effect of serotonin (5-HT) manipulations. 5-HT modulation phMRI studies show the involvement of 5-HT in a broad range of neural processes ranging from motor function through 'cold' cognition, such as memory and response inhibition, to emotional processing. We highlight findings in brain areas that show some consistency or complementarity across studies, such as the ventrolateral orbitofrontal cortex where modulation by 5-HT is task-specific, and the amygdala in emotional processing where 5-HT is predominantly inhibitory. 5-HT challenge phMRI is promising but as yet few studies have been carried out. New ways of analysing phMRI data include connectivity analysis which holds the promise of going beyond identifying isolated areas of activation/modulation to understanding functional circuits and their neurochemistry. 5-HT phMRI now needs to be taken into patient populations and methods of investigating treatment effects need to be developed. If this is successful then phMRI will provide a genuinely exciting opportunity for the rapid development of better treatments for psychiatric conditions.

Effect of quinolinic acid-induced lesions of the nucleus accumbens core on performance on a progressive ratio schedule of reinforcement: implications for inter-temporal choice.

RATIONALE: The nucleus accumbens core (AcbC) is believed to contribute to the control of operant behaviour by reinforcers. Recent evidence suggests that it is not crucial for determining the incentive value of immediately available reinforcers, but is important for maintaining the values of delayed reinforcers. OBJECTIVE: This study aims to examine the effect of AcbC lesions on performance on a progressive-ratio schedule using a quantitative model that dissociates effects of interventions on motor and motivational processes (Killeen 1994 Mathematical principles of reinforcement. Behav Brain Sci 17:105-172). MATERIALS AND METHODS: Rats with bilateral quinolinic acid-induced lesions of the AcbC (n = 15) or sham lesions (n = 14) were trained to lever-press for food-pellet reinforcers under a progressive-ratio schedule. In Phase 1 (90 sessions) the reinforcer was one pellet; in Phase 2 (30 sessions), it was two pellets; in Phase 3, (30 sessions) it was one pellet. RESULTS: The performance of both groups conformed to the model of progressive-ratio performance (group mean data: r2 > 0.92). The motor parameter, delta, was significantly higher in the AcbC-lesioned than the sham-lesioned group, reflecting lower overall response rates in the lesioned group. The motivational parameter, a, was sensitive to changes in reinforcer size, but did not differ significantly between the two groups. The AcbC-lesioned group showed longer post-reinforcement pauses and lower running response rates than the sham-lesioned group. CONCLUSIONS: The results suggest that destruction of the AcbC impairs response capacity but does not alter the efficacy of food reinforcers. The results are consistent with recent findings that AcbC lesions do not alter sensitivity to reinforcer size in inter-temporal choice schedules.

Effect of disconnecting the orbital prefrontal cortex from the nucleus accumbens core on inter-temporal choice behaviour: a quantitative analysis.

Previous experiments showed that destruction of the orbital prefrontal cortex (OPFC) or the nucleus accumbens core (AcbC) in rats altered choice between two delayed food reinforcers. Application of a quantitative model of inter-temporal choice suggested that lesions of either structure increased the delay-dependent degradation of reinforcer value (delay discounting); destruction of the OPFC (but not the AcbC) also increased the relative value of the larger reinforcer. This experiment examined the effect of disconnecting the OPFC from the AcbC on inter-temporal choice. Rats received excitotoxin-induced contralateral lesions of the OPFC and AcbC (disconnection), severing of the anterior corpus callosum (callosotomy), a combined lesion (disconnection+callosotomy) or sham lesions. They were trained in a discrete-trials progressive delay schedule to press levers A and B for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after a delay d(B). d(B) increased across blocks of trials; d(A) was manipulated across phases of the experiment. Indifference delay, d(B50) (value of d(B) corresponding to 50% choice of B), was estimated for each rat in each phase, and linear indifference functions (d(B50)vs. d(A)) were derived. The disconnection+callosotomy group showed a lower intercept of the indifference function (implying a higher rate of delay discounting) than the sham-lesioned group; the disconnection group showed a similar but less robust effect, whereas the callosotomy group did not differ significantly from the sham-lesioned group. The results suggest that OPFC-AcbC connections are involved in delay discounting of food reinforcers, but provide no evidence for an involvement of OPFC-AcbC connections in regulating sensitivity to reinforcer size.

Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines.

A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.

Effects of quinolinic acid-induced lesions of the nucleus accumbens core on inter-temporal choice: a quantitative analysis.

RATIONALE: There is evidence that lesions of the nucleus accumbens core (AcbC) promote preference for smaller earlier reinforcers over larger delayed reinforcers in inter-temporal choice paradigms. It is not known whether this reflects an effect of the lesion on the rate of delay discounting, on sensitivity to reinforcer magnitude, or both. AIM: We examined the effect of AcbC lesions on inter-temporal choice using a quantitative method that allows effects on delay discounting to be distinguished from effects on sensitivity to reinforcer size. MATERIALS AND METHODS: Sixteen rats received bilateral quinolinic acid-induced lesions of the AcbC; 14 received sham lesions. They were trained under a discrete-trials progressive delay schedule to press two levers (A and B) for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after d(B). d(B) increased across blocks of trials, while d(A) was manipulated across phases of the experiment. Indifference delay d(B(50)) (value of d(B) corresponding to 50% choice of B) was estimated in each phase, and linear indifference functions (d(B(50)) vs d(A)) derived. RESULTS: d(B(50)) increased linearly with d(A) (r(2) > 0.95 in each group). The intercept of the indifference function was lower in the lesioned than the sham-lesioned group; slope did not differ between groups. The lesioned rats had extensive neuronal loss in the AcbC. CONCLUSIONS: The results confirm that lesions of the AcbC promote preference for smaller, earlier reinforcers and suggest that this reflects an effect of the lesion on the rate of delay discounting.

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress.

One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression- and anxiety-related phenotypes. In addition, a Bayesian systems-based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

Association of ATP6V1B2 rs1106634 with lifetime risk of depression and hippocampal neurocognitive deficits: possible novel mechanisms in the etiopathology of depression.

Current understanding and treatment of depression is limited to the monoaminergic theory with little knowledge of the involvement of other cellular processes. Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. We investigated the effect of rs1106634 of the ATPV1B2 gene encoding the vacuolar H+ATPase on lifetime and current depression and the possible mediating role of neuroticism by logistic and linear regression in a white European general sample of 2226 subjects. Association of rs1106634 with performance on frontal (Stockings of Cambridge (SOC)) and hippocampal-dependent (paired associates learning (PAL)) cognitive tasks was investigated in multivariate general linear models in a smaller subsample. The ATP6V1B2 rs1106634 A allele had a significant effect on lifetime but not on current depression. The effect of the A allele on lifetime depression was not mediated by neuroticism. The A allele influenced performance on the PAL but not on the SOC test. We conclude that the effects of variation in the vacuolar ATPase may point to a new molecular mechanism that influences the long-term development of depression. This mechanism may involve dysfunction specifically in hippocampal circuitry and cognitive impairment that characterizes recurrent and chronic depression.

Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms.

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.

Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression.

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development.

Structure, microstructure, and magnetism in ferrimagnetic bioceramics.

The structural and magnetic properties of ferrimagnetic bioglass ceramics in the system [0.45(CaO,P2O5)(0.52 - x)SiO2 xFe2O3 0.03Na2O], x = 0.05, 0.10, 0.15, 0.20 and heat-treated at the temperature range 600-1100 degrees C are assessed. The structure and microstructure of the samples are characterized with X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Calcium phosphate and magnetite develop as the two major crystalline phases. For x = 0.10 and 0.20, calcium phosphate undergoes a gradual transition from the monoclinic to the rhombohedral crystal system (SG P21/a-->R3c) as the heat-treatment temperature increases from 800 to 1100 degrees C. Dendrites of iron oxide with crystallites of various sizes are observed to form within a glassy matrix enriched in calcium, phosphorous, and silicon. Saturation magnetization, remanence, and coercivity are found from dc magnetic measurements. They vary with the specific processing parameters of the composites, and these are correlated with the observed structure and microstructure of the materials.

The effect of orbital prefrontal cortex lesions on performance on a progressive ratio schedule: implications for models of inter-temporal choice.

In a previous experiment [Kheramin S, Body S, Mobini S, Ho M-Y, Velazquez-Martinez DN, Bradshaw CM, et al. Effects of quinolinic acid-induced lesions of the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis. Psychopharmacology 2002;165: 9-17], destruction of the orbital prefrontal cortex (OPFC) in rats altered choice between two delayed food reinforcers, enhancing preference for the larger reinforcer. Theoretical analysis based on a quantitative model of inter-temporal choice [Ho M-Y, Mobini S, Chiang T-J, Bradshaw CM, Szabadi E. Theory and method in the quantitative analysis of 'impulsive choice' behaviour: implications for psychopharmacology. Psychopharmacology 1999;146:362-72] indicated that the lesion had increased the relative value of the larger of the two reinforcers due to a general reduction of absolute reinforcer value. The present experiment tested this hypothesis using a reinforcement schedule that did not entail either explicit choice or delayed reinforcement. Ten rats received quinolinic acid-induced lesions of the OPFC, and ten rats received sham lesions. The rats were trained under a progressive-ratio schedule of food reinforcement for 60 daily sessions. Response rates in successive ratios were a bitonic (inverted-U) function of ratio size. Analysis of the data using a three-parameter equation derived from a quantitative model of ratio schedule performance [Killeen PR. Mathematical principles of reinforcement. Behav. Brain Sci. 1994;17:105-72] revealed that the parameter specifying hypothetical reinforcer value was significantly lower in the OPFC-lesioned group than in the sham-lesioned group, consistent with the hypothesis that destruction of the OPFC resulted in devaluation of the food reinforcer.

Lack of behavioural effects after acute tyrosine depletion in healthy volunteers.

Acute dietary tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture (TP-). The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the TP- occasion (-78.7%, p < 0.0001) and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions (p < 0.02). Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function.