Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs.

BACKGROUND: Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far. METHODS: To fill this gap, we conducted a cross-sectional study combining clinical and dual-tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([11 C]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane) ([11 C]PE2I) and serotonin ([11 C]-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine) ([11 C]DASB) reuptake, after different durations of Parkinson's disease (ie, in short-disease duration drug-naive de novo (n = 27, 0-2 years-duration), suffering from apathy (n = 14) or not (n = 13); intermediate-disease duration (n = 15, 4-7 years-duration) and long-disease duration, non-demented (n = 15, 8-10 years-duration) patients). Fifteen age-matched healthy subjects were also enrolled. RESULTS: The main findings are threefold: (1) both dopaminergic and serotonergic lesions worsen with the duration of Parkinson's disease, spreading from midbrain/subcortical to cortical regions; (2) the presence of apathy at PD onset is associated with more severe cortical and subcortical serotonergic and dopaminergic disruption, similar to the denervation pattern observed in intermediate-disease duration patients; and (3) the severity of parkinsonian apathy, depression, and trait-anxiety appears primarily related to serotonergic alteration within corticostriatal limbic areas. CONCLUSIONS: Altogether, these findings highlight the prominent role of serotonergic degeneration in the expression of several neuropsychiatric symptoms occurring after different durations of Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society.

Wait and you shall see: sexual delay discounting in hypersexual Parkinson's disease.

Patients with Parkinson's disease may develop impulse control disorders under dopaminergic treatments. Impulse control disorders include a wide spectrum of behaviours, such as hypersexuality, pathological gambling or compulsive shopping. Yet, the neural systems engaged in specific impulse control disorders remain poorly characterized. Here, using model-based functional MRI, we aimed to determine the brain systems involved during delay-discounting of erotic rewards in hypersexual patients with Parkinson's disease (PD+HS), patients with Parkinson's disease without hypersexuality (PD - HS) and controls. Patients with Parkinson's disease were evaluated ON and OFF levodopa (counterbalanced). Participants had to decide between two options: (i) wait for 1.5 s to briefly view an erotic image; or (ii) wait longer to see the erotic image for a longer period of time. At the time of decision-making, we investigated which brain regions were engaged with the subjective valuation of the delayed erotic reward. At the time of the rewarded outcome, we searched for the brain regions responding more robustly after waiting longer to view the erotic image. PD+HS patients showed reduced discounting of erotic delayed rewards, compared to both patients with Parkinson's disease and controls, suggesting that they accepted waiting longer to view erotic images for a longer period of time. Thus, when using erotic stimuli that motivate PD+HS, these patients were less impulsive for the immediate reward. At the brain system level, this effect was paralleled by the fact that PD+HS, as compared to controls and PD - HS, showed a negative correlation between subjective value of the delayed reward and activity of medial prefrontal cortex and ventral striatum. Consistent with the incentive salience hypothesis combining learned cue-reward associations with current relevant physiological state, dopaminergic treatment in PD+HS boosted excessive 'wanting' of rewards and heightened activity in the anterior medial prefrontal cortex and the posterior cingulate cortex, as reflected by higher correlation with subjective value of the option associated to the delayed reward when ON medication as compared to the OFF medication state. At the time of outcome, the anterior medial prefrontal/rostral anterior cingulate cortex showed an interaction between group (PD+HS versus PD - HS) and medication (ON versus OFF), suggesting that dopaminergic treatment boosted activity of this brain region in PD+HS when viewing erotic images after waiting for longer periods of time. Our findings point to reduced delay discounting of erotic rewards in PD+HS, both at the behavioural and brain system levels, and abnormal reinforcing effect of levodopa when PD+HS patients are confronted with erotic stimuli.10.1093/brain/awy298_video1awy298media15983845074001.

What do error patterns in processing facial expressions, social interaction scenes and vocal prosody tell us about the way social cognition works in children with 22q11.2DS?

Impairments in social cognition have been frequently described in 22q11.2 deletion syndrome (22q11.2DS) and are thought to be a hallmark of difficulties in social interactions. The present study addresses aspects that are critical for everyday social cognitive functioning but have received little attention so far. Sixteen children with 22q11.2DS and 22 controls completed 1 task of facial expression recognition, 1 task of attribution of facial expressions to faceless characters involved in visually presented social interactions, and 1 task of attribution of facial expressions to characters involved in aurally presented dialogues. All three tasks have in common to involve processing of emotions. All participants also completed two tasks of attention and two tasks of visual spatial perception, and their parents completed some scales regarding behavioural problems of their children. Patients performed worse than controls in all three tasks of emotion processing, and even worse in the second and third tasks. However, they performed above chance level in all three tasks, and the results were independent of IQ, age and gender. The analysis of error patterns suggests that patients tend to coarsely categorize situations as either attractive or repulsive and also that they have difficulties in differentiating emotions that are associated with threats. An isolated association between the tasks of emotion and behaviour was found, showing that the more frequently patients with 22q11.2DS perceive happiness where there is not, the less they exhibit aggressive behaviour.

Computer-based cognitive remediation program for the treatment of behavioral problems in children with intellectual disability: the «COGNITUS & MOI¼ study protocol for a randomized controlled trial.

BACKGROUND: Comorbid psychiatric disorders are frequent in children with intellectual disability (ID). Given the limitations of drugs treatments, cognitive remediation could be a promising tool to reduce these challenging behaviors but evidence is still scarce. Our group recently developed the «COGNITUS & MOI¼ program that is designed to train the attentional and visuospatial skills in children with ID. This study investigates the efficiency of the «COGNITUS & MOI¼ program in this condition. METHODS: Children (age: 6.00-13.11) with mild to moderate ID and behavioral problems, will benefit from a therapy during a 16 week randomized controlled trial. One group will be randomly treated with the «COGNITUS & MOI¼ program and the other with a motor skill and video viewing intervention. All participants will undergo a behavioral, functional and neurocognitive assessment at baseline, post-intervention, and 6-month follow-up. Primary outcome will be the change from the baseline of the score on the "hyperactivity - noncompliance" subscale of the Aberrant Behavior Checklist. DISCUSSION: If the results are conclusive, the «COGNITUS & MOI¼ program could be added to the therapeutic arsenal against challenging behavior in children with ID. TRIAL REGISTRATION: ClinicalTrials NCT02797418 . Date registered: 8th of June 2016.

The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson's disease.

SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ -21) and 15 non-apathetic (-36 ≤ Lille Apathy Rating Scale scores ≤ -22) drug-naïve de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [(11)C-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane (PE2I)] (n = 29) and serotonergic [(11)C-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine (DASB)] (n = 27) presynaptic transporter radioligands. Apathetic parkinsonian patients presented higher depression (P = 0.0004) and anxiety (P = 0.004) scores - as assessed using the Beck Depression Inventory and the part B of the State-Trait Anxiety Inventory, respectively - compared to the non-apathetic ones - who were not different from the age-matched healthy subjects (n = 15). Relative to the controls, the non-apathetic parkinsonian patients mainly showed dopaminergic denervation (n = 14) within the right caudate nucleus, bilateral putamen, thalamus and pallidum, while serotonergic innervation (n = 15) was fairly preserved. Apathetic parkinsonian patients exhibited, compared to controls, combined and widespread dopaminergic (n = 15) and serotonergic (n = 12) degeneration within the bilateral caudate nuclei, putamen, ventral striatum, pallidum and thalamus, but also a specific bilateral dopaminergic disruption within the substantia nigra-ventral tegmental area complex, as well as a specific serotonergic alteration within the insula, the orbitofrontal and the subgenual anterior cingulate cortices. When comparing the two parkinsonian groups, the apathetic patients mainly displayed greater serotonergic alteration in the ventral striatum, the dorsal and the subgenual parts of the anterior cingulate cortices, bilaterally, as well as in the right-sided caudate nucleus and the right-sided orbitofrontal cortex. Regression analyses also revealed that the severity of apathy was moreover mainly related to specific serotonergic lesions within the right-sided anterior caudate nucleus and the orbitofrontal cortex, while the degree of both depression and anxiety was primarily linked to serotonergic disruption within the bilateral subgenual parts and/or the right dorsal part of the anterior cingulate cortex, without prominent role of the dopaminergic degeneration in the pathogenesis of these three non-motor signs. Altogether, these findings highlight a prominent role of the serotonergic degeneration in the expression of the neuropsychiatric symptoms occurring at the onset of Parkinson's disease.

Cognitive Abilities of Children With Neurological and Liver Forms of Wilson Disease.

Cognitive impairment in adult patients experiencing Wilson disease is now more clearly described, even in liver forms of the disease. Although this condition can appear during childhood, the cognitive abilities of children have not yet been reported in a substantial case series. This retrospective study included 21 children with Wilson disease who had undergone general cognitive assessment. The results argue in favor of a poor working memory capacity in the liver form of the disease, and more extensive cognitive impairments in its neurological form. Extensive neuropsychological investigations on all children experiencing Wilson disease are thus required.

Extent of magnitude representation deficit and relationship with arithmetic skills in children with 22q11.2DS.

BACKGROUND: Previous studies have produced conflicting results concerning the extent of magnitude representation deficit and its relationship with arithmetic achievement in children with 22q11.2 deletion syndrome. More specifically, it remains unclear whether deficits are restricted to visuospatial content or are more general and whether they could explain arithmetical impairment. METHODS: Fifteen 5- to 12-year-old children with 22q11.2 deletion syndrome and 23 age-matched healthy controls performed a non-symbolic magnitude comparison task. Depending on the trial, participants had to compare stimuli with high or low visuospatial load (visuospatial stimuli or temporal sequence of visual stimuli). The participants also completed a battery of arithmetic skills (ZAREKI-R) and a battery of global cognitive functioning (WISC-V or WPPSI-IV), from which working memory and visuospatial indices were derived. RESULTS: Children with 22q11.2DS responded as fast as healthy controls did but received fewer correct responses, irrespective of visuospatial load. In addition, their performance in the non-symbolic magnitude comparison task did not correlate with the ZAREKI total score, while the working memory index did. CONCLUSION: Children with 22q11.2DS might suffer from a global magnitude representation deficit rather than a specific deficit due to visuospatial load. However, this deficit alone does not seem to be related to arithmetic achievement. Working memory might be a better concern of interest in favoring arithmetic skills in patients with 22q11.2 deletion syndrome. TRIAL REGISTRATION: Clinicaltrials, NCT04373226 . Registered 16 September 2020.

How emotional pictures influence visuospatial binding in short-term memory in ageing and Alzheimer's disease?

The present study examines the prediction that emotion can facilitate short-term memory. Nevertheless, emotion also recruits attention to process information, thereby disrupting short-term memory when tasks involve high attentional resources. In this way, we aimed to determine whether there is a differential influence of emotional information on short-term memory in ageing and Alzheimer's disease (AD). Fourteen patients with mild AD, 14 healthy older participants (NC), and 14 younger adults (YA) performed two tasks. In the first task, involving visual short-term memory, participants were asked to remember a picture among four different pictures (negative or neutral) following a brief delay. The second task, a binding memory task, required the recognition by participants of a picture according to its spatial location. The attentional cost involved was higher than for the first task. The pattern of results showed that visual memory performance was better for negative stimuli than for neutral ones, irrespective of the group. In contrast, binding memory performance was essentially poorer for the location of negative pictures in the NC group, and for the location of both negative and neutral stimuli in the AD group, in comparison to the YA group. Taken together, these results show that emotion has beneficial effects on visual short-term memory in ageing and AD. In contrast, emotion does not improve their performances in the binding condition.

Exploratory case study of monozygotic twins with 22q11.2DS provides further clues to circumscribe neurocognitive markers of psychotic symptoms.

Variation in facial emotion processing abilities may contribute to variability in penetrance for psychotic symptoms in 22q11.2DS. However, the precise nature of the social cognitive dysfunction (i.e., facial expression perception vs. emotion recognition), the potential additional roles of genetic and environmental variabilities, and consequently the possibility of using this neurocognitive marker in clinical monitoring remain unclear. The present case study aimed at testing the hypothesis that when confounding factors are controlled, the presence of psychotic symptoms in 22q11.2DS is associated, at the individual level, with a neural marker of facial expression perception rather than explicit emotional face recognition. Two monozygotic twins with 22q11.2DS discordant for psychiatric manifestations performed (1) a classical facial emotion labelling task and (2) an implicit neural measurement of facial expression perception using a frequency-tagging approach in electroencephalography (EEG). Analysis of the periodic brain response elicited by a change of facial expression from neutrality indicated that the twin with psychotic symptoms did not detect emotion among neutral faces while the twin without the symptoms did. In contrast, both encountered difficulties labelling facial emotion. The results from this exploratory twin study support the idea that impaired facial expression perception rather than explicit recognition of the emotion expressed might be a neurocognitive endophenotype of psychotic symptoms that could be reliable at a clinical level. Although confirmatory studies should be required, it facilitates further discussion on the etiology of the clinical phenotype in 22q11.2DS.

An implicit and reliable neural measure quantifying impaired visual coding of facial expression: evidence from the 22q11.2 deletion syndrome.

Although various psychiatric disorders present with social-cognitive impairment, a measure assessing social-cognitive processes implicitly and reliably, with high selectivity and with enough signal-to-noise ratio (SNR) for individual evaluation of any population at any age, is lacking. Here we isolate a neural marker quantifying impaired visual coding of facial expression in individuals with 22q11.2 deletion syndrome (22q11DS) using frequency-tagging with electroencephalography (EEG). Twenty-two 22q11DS participants and 22 healthy controls were presented with changes of facial expression displayed at low, moderate, and high intensities every five cycles in a stream of one neutral face repeating 6 times per second (i.e., at a 6 Hz base rate). The brain response to expression changes tagged at the 1.2 Hz (i.e., 6 Hz/5) predefined frequency was isolated over occipito-temporal regions in both groups of participants for moderate- and high-intensity facial expressions. Neural sensitivity to facial expression was reduced by about 36% in 22q11DS, revealing impaired visual coding of emotional facial signals. The significance of the expression-change response was estimated for each single participant thanks to the high SNR of the approach. Further analyses revealed the high reliability of the response and its immunity from other neurocognitive skills. Interestingly, response magnitude was associated with the severity of positive symptoms, pointing to a potential endophenotype for psychosis risk. Overall, the present study reveals an objective, selective, reliable, and behavior-free signature of impaired visual coding of facial expression implicitly quantified from brain activity with high SNR. This novel tool opens avenues for clinical practice, providing a potential early biomarker for later psychosis onset and offering an alternative for individual assessment of social-cognitive functioning in even difficult-to-test participants.

12q13.12q13.13 microdeletion encompassing ACVRL1 and SCN8A genes: Clinical report of a new contiguous gene syndrome.

Hereditary hemorrhagic telangiectasia is usually linked to the presence of a pathogenic mutation ACVRL1 or ENG. Thus, apparently there is no benefit to perform an array CGH in case of HHT. However, ENG has been involved in a contiguous gene syndrome due to a de novo 9q33.3q34.11 microdeletion. We describe here a new contiguous gene syndrome involving ACVRL1 gene. A 50-year-old female patient had a typical clinical presentation of hereditary hemorrhagic telangiectasia (HHT) with epistaxis, cutaneous-mucous telangiectases, arteriovenous malformation. She also presented a cognitive disability. Cognitive assessment showed a heterogeneous cognitive disorder predominating in the executive sphere without intellectual deficiency. She had no peculiar morphological feature. Neurological examination disclosed the presence of contralateral mirror movements during voluntary movement of each hand. A heterozygous deletion of the whole ACVRL1 gene (exons 1 to 10) was found to be responsible for the HHT features. To investigate further the dysexecutive syndrome and the mirror movements, we performed oligonucleotide array comparative genomic hybridization (array CGH) study (180K, Agilent, Santa-Clara, CA, USA). This study revealed a de novo 1.58 Mb deletion on chromosome 12q13.12q13.13 encompassing the ACVRL1 and SCN8A genes. To our knowledge, this deletion has not been previously reported and defines a new contiguous gene syndrome. The loss of one ACVRL1 allele is likely to be responsible for the HHT phenotype, while the deletion of the SCN8A gene is likely to be the cause of the mild cognitive disorder. SCN8A haploinsufficiency might also be involved in the occurrence of mirror movements. This report highlights the benefit of searching for large rearrangements in cases including unusual symptoms in association with HHT. On the other hand, an early diagnosis of 12q13.12q13.13 microdeletion based on the presence of a dysexecutive syndrome and/or mirror movement may allow to prevent HHT complications.

Overview of Social Cognitive Dysfunctions in Rare Developmental Syndromes With Psychiatric Phenotype.

Rare neurodevelopmental syndromes often present social cognitive deficits that may underlie difficulties in social interactions and increase the risk of psychosis or autism spectrum disorders. However, little is known regarding the specificities of social cognitive impairment across syndromes while it remains a major challenge for the care. Our review provides an overview of social cognitive dysfunctions in rare diseases associated with psychiatric symptoms (with a prevalence estimated between 1 in 1,200 and 1 in 25,000 live births: 22q11.2 deletion syndrome, Angelman syndrome, Fragile X syndrome, Klinefelter syndrome, Prader-Willi syndrome, Rett syndrome, Smith-Magenis syndrome, Turner syndrome, and Williams syndrome) and shed some light on the specific mechanisms that may underlie these skills in each clinical presentation. We first detail the different processes included in the generic expression "social cognition" before summarizing the genotype, psychiatric phenotype, and non-social cognitive profile in each syndrome. Then, we offer a systematic review of the social cognitive abilities and the disturbed mechanisms they are likely associated with. We followed the PRISMA process, including the definition of the relevant search terms, the selection of studies based on clear inclusion, and exclusion criteria and the quality appraisal of papers. We finally provide insights that may have considerable influence on the development of adapted therapeutic interventions such as social cognitive training (SCT) therapies specifically designed to target the psychiatric phenotype. The results of this review suggest that social cognition impairments share some similarities across syndromes. We propose that social cognitive impairments are strongly involved in behavioral symptoms regardless of the overall cognitive level measured by intelligence quotient. Better understanding the mechanisms underlying impaired social cognition may lead to adapt therapeutic interventions. The studies targeting social cognition processes offer new thoughts about the development of specific cognitive training programs, as they highlight the importance of connecting neurocognitive and SCT techniques.

Social cognition in Wilson's disease: A new phenotype?

Studies focusing on neuropsychological impairments in Wilson's disease (WD) have highlighted that patients showing neurological signs present significant deficits in a wide range of cognitive domains. Attentional and executive impairments have also been described in people with hepatic WD. However, social cognition abilities, i.e. cognitive processes required to perceive the emotions, intentions and dispositions of other people, have not been clearly investigated in WD. In this study we examined the social cognitive functioning in 19 patients with WD depending on their clinical status-Neurological versus Non-Neurological ("hepatic") forms-compared to 20 healthy controls. For the very first time, results highlighted that patients with WD had significant impairments in the three major components of social cognition: emotion recognition, Theory of Mind and attributional style. However, these deficits differ depending on the form of the disease: patients with neurological signs showed a wide range of deficits in the three components that were assessed-results notably revealed impairments in recognizing "fear", "anger", and "disgust", a significant Theory of Mind deficit and an "aggression bias"-whereas Non-Neurological patients only showed deficits on test assessing attributional bias, with a trend to react more "aggressively" to ambiguous social situations than healthy controls, as observed in Neurological WD patients, and a specific impairment in "anger" recognition. Our findings are discussed in the light of both neurocognitive impairments and brain damages, and especially those affecting the basal ganglia, as observed in people with WD.

Interaction of noradrenergic pharmacological manipulation and subthalamic stimulation on movement initiation control in Parkinson's disease.

BACKGROUND: Slowness in movement initiation (akinesia) is a cardinal feature of Parkinson's disease (PD), which is still poorly understood. Notably, akinesia is restored by subthalamic nucleus deep brain stimulation (STN-DBS) but not fully reversed by current dopaminergic treatments. It was recently suggested that this disorder is of executive nature (related to inhibitory control of response) and of non-dopaminergic origin (possibly noradrenergic). OBJECTIVE: To test the double hypothesis that: 1) the ability to control movement initiation is modified by noradrenergic neurotransmission modulation, and 2) this effect is mediated by the regulation of STN activity. METHODS: Sixteen STN-DBS PD patients were enrolled in a placebo-controlled study investigating the effects of noradrenergic attenuation by clonidine (∝2-adrenergic receptor agonist). Movement initiation latency was assessed by means of a cue-target reaction time task. Patients, who remained on their chronic dopaminergic medication, were tested on four sessions: two with placebo (ON- or OFF-DBS), and two with a 150 µg oral dose of clonidine (ON- or OFF-DBS). RESULTS: In the OFF stimulation condition, patients were locked into a mode of control maintaining inappropriate response inhibition. This dysfunctional executive setting was overcome by STN-DBS. Clonidine, however, was found to impair specifically the ability to release inhibitory control in the ON-DBS state. CONCLUSIONS: Overall our results suggest an important implication of the noradrenergic system in the pathophysiology of akinesia in PD. Reducing the noradrenergic "tonus" may even block the positive action of STN-DBS on akinesia, suggesting, at least by part, a noradrenergic-dependent STN-DBS efficiency.

Deep brain stimulation of the subthalamic nucleus, but not dopaminergic medication, improves proactive inhibitory control of movement initiation in Parkinson's disease.

Slowness in movement initiation is a cardinal feature of Parkinson's disease (PD) that is still poorly understood and unsuccessfully alleviated by standard therapies. Here, we raise this major clinical issue within the framework of a novel theoretical model that allows a better understanding of the basic mechanisms involved in movement initiation. This model assumes that movement triggering is inhibited by default to prevent automatic responses to unpredictable events. We investigated to which extent the top-down control necessary to release this locking state before initiating actions is impaired in PD and restored by standard therapies. We used a cue-target reaction time task to test both the ability to initiate fast responses to targets and the ability to refrain from reacting to cues. Fourteen patients with dopaminergic (DA) medication and 11 with subthalamic nucleus (STN) stimulation were tested on and off treatment, and compared with 14 healthy controls. We found evidence that patients withdrawn from treatment have trouble voluntarily releasing proactive inhibitory control; while DA medication broadly reduces movement initiation latency, it does not reinstate a normal pattern of movement initiation; and stimulation of the STN specifically re-establishes the efficiency of the top-down control of proactive inhibition. These results suggest that movement initiation disorders that resist DA medication are due to executive, not motor, dysfunctions. This conclusion is discussed with regard to the role the STN may play as an interface between non-DA executive and DA motor systems in cortico-basal ganglia loops.

Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune response to unrelated antigens.

The HIV-1 Tat protein is able to raise a humoral immune response in the absence of adjuvant. Here, we investigated whether this property can be transferred to unrelated antigens. We first observed that Tat self-adjuvanticity is a T cell-dependent phenomenon in which a Th2 profile predominates. Then, we showed that the determinant governing the property is located in the region 1-57 of Tat and that fragment Tat1-57 can make two unrelated model antigens immunogenic in the absence of adjuvant. We found a Th2 pattern of immune response for both antigens, suggesting that Tat1-57 mediates this response. Next, we showed that, although less efficient than Tat1-57, the Tat37-57 fragment suffices to transfer the adjuvant property to other antigens. We also observed that preservation of cysteine 37 is absolutely required for the transfer, suggesting the role of disulphide-mediated dimerization in the transfer of the adjuvant property. Our observations suggest that for various antigens, the use of Tat37-57 or Tat1-57 or Tat22-57C(22-34)A might represent an alternative to adjuvants in humans, thereby opening up new perspectives in vaccination.