Changes in glucose metabolism due to aging and gender-related differences in the healthy human brain

Using [(18)F]fluoro-deoxy-glucose-PET, we studied relative metabolic changes due to age- and gender-related differences in the brain of 126 healthy subjects from their twenties to seventies. We used a data-extraction technique, the three-dimensional stereotactic surface projections (3D-SSP) method, to measure metabolic changes with fewer effects of regional anatomic variances. Simple regression analysis revealed significant age-related increases in relative metabolic values in the parahippocampal and amygdala regions in both sexes in their twenties to forties, and significant age-related decreases in both sexes in their fifties to seventies. Relative values in the frontal lobe showed significant age-related decreases in both sexes in their twenties to forties, but these effects were not seen in subjects in their fifties to seventies. Significant gender differences in correlation coefficients of relative values with age were shown in the parahippocampal, primary sensorimotor, temporal, thalamus and vermis regions in subjects in their 20s to 40s, but disappeared in subjects in their twenties to forties, but were not apparent in subjects in their fifties to seventies except in the vermis. Males in their twenties to sixties and females in their fifties showed significant laterality in relative values in the temporal lobes. Our study demonstrated age- and gender-related differences in glucose metabolism in healthy subjects.     

Effects of brief cognitive-behavioral interventions on confidence to resist the urges to use heroin and methamphetamine in relapse-related situations

The aim of this study was to examine the effect of brief cognitive-behavioral (C-B) intervention on improving confidence in managing situations related to heroin and methamphetamine (MAMP) use in drug users. The subjects in the intervention group received a five-session C-B intervention, which focused on the acquisition of skills aimed at helping the subject to reduce drug use. The subjects in the intervention and control groups completed pretest and posttest assessments to determine the changes of confidence in managing situations related to drug use. A total of 70 subjects (40 heroin and 30 MAMP users) and 75 subjects (38 heroin and 37 MAMP users) in the control group completed pretest and posttest assessments. The results revealed that among heroin users, the intervention group had greater improvement in confidence to manage interpersonal situations related to heroin use than did the control group, but there was no difference in the improvement in confidence to manage intrapersonal situations between the two groups. Furthermore, MAMP users in the intervention group showed greater improvement in confidence to manage both intrapersonal and interpersonal situations related to MAMP use than the control group. The present study confirmed the efficacy of brief C-B interventions in improving confidence in ability to resist urges to use heroin and MAMP in stressful interpersonal situations and to use MAMP in intrapersonal situations. The possible explanations for the ineffectiveness of brief C-B interventions to improve confidence in managing intrapersonal situations related to heroin use are discussed.     

Impact of the neural correlates of stress and cue reactivity on stress related binge eating in the natural environment

Women with symptoms of bulimia nervosa (BN) exhibit decreased response to visual food cues in several limbic and frontal regions compared to controls. Stress causes decreased blood oxygenation level dependent (BOLD) response in these regions in non-clinical samples; there is a lack of data on this topic in BN. This study examined the impact of individual differences in neural reactivity to palatable food cues following acute stress on stress-binge trajectories in everyday life. 16 women with BN symptoms viewed palatable food cues prior to and immediately following an acute stress induction in the scanner. Participants then responded to a series of prompts assessing daily ratings of stress and binge episodes for a period of two weeks. Decreased BOLD signal was observed in response to food cues pre to post stress in the anterior cingulate cortex (ACC), amygdala, and ventromedial prefrontal cortex (vmPFC). Ecological momentary assessment data collection demonstrated that stress increased prior to binge episodes in the natural environment, and decreased following. Changes in activation in the ACC, precuneus, and dorsolateral prefrontal cortex (dlPFC) significantly moderated the relationship of stress to binge eating in daily life, such that women who exhibited decreased response reported significantly increasing stress prior to binges, while women who did not exhibit decreases reported no significant change in stress prior to binges. Individual differences in neural response to food cues under stress appear to underlie distinct antecedants to binge eating.     

Engagement in Olfaction-Related Activities is Associated with the Ability of Odor Identification and Odor Awareness

Recent research has shown that within-gender variability in olfactory abilities may be linked to sexual orientation, particularly in men, but is better predicted by childhood gender nonconformity. However, whether there could be similar within-gender variability in odor awareness remains unclear. Further, gender differences in olfactory abilities and odor awareness in favor of women have been proposed to be partly related to women’s broader olfactory experience due to their greater engagement in olfaction-related activities. Nevertheless, within-gender variability in odor exposure could also be expected. Therefore, in a sample of 156 men and women (83 non-heterosexual), we aimed to look for between- and within-gender variability in odor awareness and self-reported engagement in specific olfaction-related activities. Secondly, we tested whether interindividual (between- and within-gender) differences in olfactory abilities and odor awareness might be related to experience with odors, assessed in terms of engagement in olfaction-related activities. The results of the present study show that within-gender variability, previously found in some olfactory abilities in men and women, does not seem to extend to odor awareness, and appears to only apply to certain olfaction-related activities. In the total sample, more frequent exposure to a greater variety of potentially intense or novel food odors and flavors in both childhood and adulthood was positively linked to both greater odor awareness and better odor identification. There was also a positive link between female-stereotyped activities in childhood and odor awareness. Our results suggest that long-term everyday experience with odors may be linked to a better ability of odor identification and greater odor awareness, although longitudinal studies are needed to further investigate these associations.     

Long-term depression in vivo: effects of sex, stress, diet, and prenatal ethanol exposure

Long-term depression (LTD) of synaptic efficacy has proven a difficult phenomenon to examine in vivo, despite the ease with which it is induced in a variety of in vitro preparations. Prior exposure to an acute stressful episode does however seem to enhance the capacity of the hippocampus to exhibit LTD in vivo in male animals. In the present experiments, we examined the capacity for low-frequency stimuli (low-frequency stimulation (LFS)) to induce LTD in juvenile male and female animals following an acute stress episode. Interestingly, prior exposure to stress was only required for the induction of LTD in male animals, while both control and stressed female animals exhibited equivalent LTD. In animals that were exposed to ethanol in utero, a similar requirement for prior exposure to stress to elicit LTD was found for male, but not female animals. This prenatal ethanol exposure did not in itself alter the capacity for LTD induction in either sex; however, in utero food restriction did enhance LTD induction in both male and female animals, irrespective of whether they were exposed to stress just prior to being administered LFS. These results indicate that in utero dietary restriction more drastically affects CA1 LTD than in utero ethanol exposure. In addition, female animals seem to exhibit LTD in vivo in the absence of stress much more easily than their male counterparts.     

Cerebral palsy rates among low-birthweight infants fell in the 1990s

Using a population-based register, this study sought to ascertain changes in the rate and severity of cerebral palsy (CP) in a geographically defined area of the UK among infants weighing less than 1500 g and born between 1984 and 1995. There were 417414 live births in the area, which included Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. Of the 898 children with CP (526 males, 372 females), 194 (21.6%) weighed less than 1500 g at birth. The overall CP rate for neonatal survivors fell from 2.5 out of every 1000 in 1984 to 1986 to 1.7 in 1993 to 1995. The rate for those weighing less than 1000 g rose to 90 out of every 1000 neonatal survivors in 1987 to 1989 and then fell to 57 in 1993 to 1995. A similar pattern is seen among infants weighing 1000 to 1499 g at birth, the rate rising to 77 in 1987 to 1988 and then falling to 40 in 1993 to 1995. The rate of severe motor disability among infants weighing less than 1500 g also decreased (24.6 in 1984-1986 to 12.5 in 1993-1995). The relation of these findings to changes in perinatal care in the early 1990s is not known.     

Regional trends in cerebrovascular mortality in Germany after unification (1990-1999)

BACKGROUND AND PURPOSE: After the unification in 1990 two different health and political systems merged in Germany. Our aim was to analyze trends in mortality from cerebrovascular diseases in the formerly divided western and eastern parts of Germany since the unification. METHODS: Trends in mortality were determined by analyzing age-adjusted vital statistics data obtained from the Federal Statistics Office. ICD-9 was used from 1990 to 1997 and ICD-10 in 1998 and 1999. RESULTS: Cerebrovascular mortality declined in Germany between 1991 and 1999 from 104.4 to 72.3 per 100000 men and from 82.2 to 55.5 per 100000 women. Mortality rates from cerebrovascular diseases in East Germany were continuously above West German rates: in 1991 the overall rate ratio in East compared to West Germany was 1.6 and in 1999 it was 1.5 in both men and women. This regional variation is mainly due to a higher rate of cerebrovascular diseases being defined as 'Other' (ICD-9 437, now ICD-10 I67) in East compared to West Germany. CONCLUSION: Nearly 10 years after the unification, cerebrovascular mortality is still markedly higher in East compared to the West Germany. Further investigation is needed to determine the causes for the regional variation in cerebrovascular mortality and to improve preventive strategies.     

Response to levodopa treatment in dopa-responsive dystonia

BACKGROUND: Dopa-responsive dystonia (DRD) is similar to Parkinson disease in that both disorders have impaired dopamine synthesis and respond to levodopa treatment. Dopa-responsive dystonia differs in that dopamine storage is intact in contrast to Parkinson disease in which it is markedly reduced. OBJECTIVE: To examine the short- and long-duration responses to levodopa dosing in subjects with DRD. METHODS: The response to brief infusions of levodopa was examined in 4 subjects with DRD and the effects of withdrawal of levodopa for 3 to 7 days studied in the 3 subjects receiving long-term levodopa therapy. Motor function was measured with tapping speed, Unified Parkinson's Disease Rating Scale motor score, and global dystonia score. RESULTS: The short-duration response to levodopa dosing seems to develop more slowly and persists longer in subjects with DRD than in subjects with Parkinson disease. Withdrawal of levodopa leads to a gradual decline in tapping speed and reemergence of dystonia over several days, similar to the rate of decay of motor function in Parkinson disease. The short- and long-duration responses were not clearly differentiated in DRD. CONCLUSIONS: This pilot study suggests that retained dopamine storage in DRD may prolong the short-duration response and blur the distinction of the short- and long-duration responses. The decline in motor function in DRD on withdrawal of long-term levodopa therapy resembles that in Parkinson disease, suggesting that a long-duration response, if it exists in DRD, is unrelated to dopamine storage.     

Cocaine effects on the developing brain: current status

The present paper reports on the results obtained in a rabbit model of prenatal cocaine exposure that mimics the pharmacokinetics of crack cocaine in humans, and relates these findings to studies in other species including humans. A general finding is that prenatal exposure to cocaine during neurogenesis produces dysfunctions in signal transduction via the dopamine D₁ receptor and alterations in cortical neuronal development leading to permanent morphological abnormalities in frontocingulate cortex and other brain structures. Differences in the precise effects obtained appear to be due to the dose, route and time of cocaine administration. Related to these effects of in utero cocaine exposure, animals demonstrate permanent deficits in cognitive processes related to attentional focus that have been correlated with impairment of stimulus processing in the anterior cingulate cortex. The long-term cognitive deficits observed in various species are in agreement with recent reports indicating that persistent attentional and other cognitive deficits are evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.     

Neonatal ventral hippocampal lesions attenuate the nucleus accumbens dopamine response to stress: an electrochemical study in the adult rat

Neonatal damage to the ventral hippocampus (VH) can lead, during adulthood, to behaviours that are believed to reflect enhanced mesocorticolimbic dopamine (DA) transmission. In the present study, the effects of neonatal excitotoxic lesions to the VH on spontaneous locomotor activity and stress-elicited increases in extracellular nucleus accumbens (NAcc) DA levels were examined in adult rats. Male pups received, on postnatal day 7, bilateral injections of either an ibotenic acid solution (lesioned) or vehicle (sham-lesioned) into the VH. At 3-4 months of age, animals were assessed during five daily sessions for changes in spontaneous locomotor activity associated with habituation to a novel environment. Voltammetry was used in separate groups of sham- and VH-lesioned animals to monitor the NAcc DA response to each of five once-daily exposures to tail-pinch stress. The results indicate that while VH-lesioned animals seem to habituate to novelty, they remain hyperactive relative to sham-lesioned controls. In contrast, however, stress consistently elicited in VH-lesioned animals smaller and shorter-lasting increases in NAcc DA than in sham-lesioned controls. These data suggest that neonatal excitotoxic damage to VH leads to changes in DA function that persist into adulthood. The blunted response to stress seen in VH-lesioned animals indicates that one consequence of such damage is a functional hyporeactivity in meso-NAcc DA neurons. The fact that these animals are spontaneously more active suggests compensatory changes in DA function that are efferent to DA terminals in NAcc.     

Cerebrovascular alterations in protein kinase C-mediated constriction in stroke-prone rats

BACKGROUND AND PURPOSE: Cerebrovascular pressure-dependent constriction may involve the smooth muscle production of diacylglycerol, which could facilitate constriction by activating protein kinase C (PKC). A dysfunctional PKC system could promote the loss of pressure-dependent constriction. We attempted to determine whether the alterations in pressure-dependent constriction in the middle cerebral arteries (MCAs) observed in relation to stroke development in Wistar-Kyoto stroke-prone spontaneously hypertensive rats (SHRsp) were associated with defects in the ability of the arteries to constrict in response to PKC activation. METHODS: MCAs were sampled from SHRsp before and after stroke development and in stroke-resistant Wistar-Kyoto spontaneously hypertensive rats. A pressure myograph was used to test the ability of the arteries to constrict in response to a 100 mm Hg pressure step and subsequently to contract in response to phorbol 12,13-dibutyrate in the presence of nifedipine (3 micromol/L). RESULTS: Pressure-dependent constriction and constriction in response to phorbol dibutyrate in the MCAs were inhibited by PKC inhibitors (staurosporine [40 nmol/L], chelerythrine [12 micromol/L], bisindolylmaleimide [5 micromol/L]), declined with age before stroke development in SHRsp, and were absent after stroke. There was a significant relationship between pressure- and phorbol dibutyrate-induced constriction (r=0.815, P<0. 05). CONCLUSIONS: Phorbol esters interact with the same activation site as diacylglycerol to stimulate PKC. An inability to constrict in response to phorbol dibutyrate may reflect unresponsiveness to diacylglycerol and may contribute to the loss of pressure-dependent constriction associated with stroke in the MCAs of SHRsp. The loss of this autoregulatory function before stroke could increase the risk of cerebral hemorrhage.     

Endogenous generation of cyanide in neuronal tissue: involvement of a peroxidase system

In a study of the mechanism by which cyanide is produced in neural tissue, it was hypothesized that nerve cells generate cyanide in a manner similar to that in leukocytes. As in white blood cells, glycine addition enhanced cyanide production in rat pheochromocytoma cells. Because myeloperoxidase catalyses cyanide production in leukocytes, a selective myeloperoxidase inhibitor (aminobenzoic acid hydrazide) was tested and found to inhibit opiate agonist-induced cyanide production in pheochromocytoma cells and also in rat brain. In addition, hydrogen peroxide enhanced cyanide release in pheochromocytoma cells, further suggesting that the process is oxidative in nature. Sonicated rat pheochromocytoma cells did not generate cyanide in response to an agonist acting on surface receptors even though disrupted cells responded to glycine. The mitochondrial fraction from rat brain produced more cyanide in response to glycine than any other fraction. Thus glycine seems to act at an intracellular site to enhance cyanide production and the process seems to involve a peroxidase mechanism similar to that reported for white blood cells.     

Neuronal activation related to auditory perception in the brain of a non-songbird, the ring dove

In songbirds, parrots, and hummingbirds, which need to learn their songs, exposure to conspecific song leads to increased expression of the immediate early gene (IEG) ZENK in a number of forebrain regions, including the caudomedial nidopallium (NCM) and the caudomedial mesopallium (CMM). Here we investigated the pattern of IEG expression in response to auditory stimulation in the brain of the ring dove (Streptopelia risoria), a non-songbird that does not need to learn its vocalizations. Ring dove males were exposed to conspecific vocalizations (coos), to heterospecific vocalizations (zebra finch song) or they were kept in silence. IEG expression was investigated by means of immunocytochemical analysis of the distribution of the ZENK protein product Zenk. In all three groups there was Zenk expression in several forebrain regions including the NCM and the CMM, similar to earlier findings in song-learning species. Quantitative analysis of the NCM, the CMM, and the hippocampus revealed significantly greater Zenk expression in birds exposed to conspecific vocalizations than in birds kept in silence, in the CMM only. These results show that there is substantial Zenk expression in the forebrain of a non-song-learning bird, comparable to that in avian song-learning taxa. These findings suggest that there is IEG expression specific to conspecific auditory stimulation in the CMM in both songbirds and non-songbirds.     

Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-making

Recent evidence has linked exposure to addictive drugs to an inability to employ information about adverse consequences, or outcomes, to control behavior. For instance, addicts and drug-experienced animals fail to adapt their behavior to avoid adverse outcomes in gambling and reversal tasks or after changes in the value of expected rewards. These deficits are similar to those caused by damage to the orbitofrontal cortex, suggesting that addictive drugs may cause long-lasting changes in the representation of outcome associations in a circuit that includes the orbitofrontal cortex. Here we test this hypothesis by recording from orbitofrontal neurons in a discrimination task in rats previously exposed to cocaine (30 mg/kg i.p. for 14 days). We found that orbitofrontal neurons recorded in cocaine-experienced rats failed to signal the adverse outcome at the time a decision was made in the task. The loss of this signal was associated with abnormal changes in response latencies on aversive trials. Furthermore, upon reversal of the cue-outcome associations, orbitofrontal neurons in cocaine-treated rats with enduring reversal impairments failed to reverse their cue-selectivity, while orbitofrontal neurons in cocaine-treated rats with normal performance showed an increase in the plasticity of cue-selective firing after reversal. These results provide direct neurophysiological evidence that exposure to cocaine can cause behaviorally relevant changes in the processing of associative information in a circuit that includes the orbitofrontal cortex.     

Previous maze experience required to increase open arms avoidance in rats submitted to the elevated plus-maze model of anxiety

Studies have shown an increased open arm avoidance in rats re-exposed to the elevated plus-maze (EPM), which suggests a qualitative shift in emotional states from an unconditioned (Trial 1) to a learned (Trial 2) form of fear response, but a precise source of aversion has not been determined. Using rats submitted to the EPM or various EPM-derived configurations, this study was designed to investigate what previous maze experiences in Trial 1 are required to increase avoidance of open arms in EPM Trial 2. Results obtained from rats submitted to the EPM or EPM-derived configurations confirmed the increased open arms avoidance in Trial 2. Rats confined to either open or enclosed arms failed to show the increased avoidance of open arms in Trial 2. The results are discussed in terms of the minimum prerequisite in Trial 1 to elicit an avoidance learning response to open arms in Trial 2, and also the implications of an acquired fear response in rats for the study of the biological basis of anxiety.     

Visual event-related potential changes in multiple system atrophy: delayed N2 latency in selective attention to a color task

Recent studies demonstrated an altered P3 component and prolonged reaction time during the visual discrimination tasks in multiple system atrophy (MSA). In MSA, however, little is known about the N2 component which is known to be closely related to the visual discrimination process. We therefore compared the N2 component as well as the N1 and P3 components in 17 MSA patients with these components in 10 normal controls, by using a visual selective attention task to color or to shape. While the P3 in MSA was significantly delayed in selective attention to shape, the N2 in MSA was significantly delayed in selective attention to color. N1 was normally preserved both in attention to color and in attention to shape. Our electrophysiological results indicate that the color discrimination process during selective attention is impaired in MSA.     

Exercise-induced changes in platelet aggregation; a comparison of whole blood and platelet rich plasma techniques

Studies have been performed to assess the effect of exercise on spontaneous platelet aggregation in shaken whole blood, and on agonist-induced platelet aggregation in whole blood and platelet rich plasma (PRP). Spontaneous platelet aggregation in shaken whole blood was increased following exercise compared to pre-exercise values. The increase in spontaneous aggregation after exercise correlated inversely with the increase in white cell count in whole blood. Platelet sensitivity in whole blood to adrenaline, collagen and adenosine diphosphate (ADP) was increased following exercise. Changes in platelet sensitivity to adrenaline following exercise correlated with increases in plasma noradrenaline levels but not with changes in blood cell counts. In PRP, platelet sensitivity to ADP and to collagen was increased following exercise when the pre and post-exercise PRP platelet counts were not corrected to allow for the increase in platelet count which occurred with exercise. When the PRP platelet counts were corrected, no changes in platelet sensitivity to any agonist after exercise were observed.     

Epileptogenic effect of hypoxia in the immature rodent brain

The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia.     

Role of paraventricular nucleus (PVH) in baroreflex-mediated changes in lumbar sympathetic nerve activity and heart rate

Electrophysiological and neuroanatomical studies indicate that reciprocal connections between the paraventricular nucleus (PVH) and medullary sites are involved in cardiovascular regulation. To determine whether the PVH is involved in the regulation of baroreflex responses, lumbar sympathetic nerve activity (LSNA) and heart rate (HR) changes were recorded in response to increases in arterial pressure (produced by bolus doses of phenylephrine i.v.) prior to, during, and 60 min following the injection of lidocaine (2% lidocaine, 200 nl) bilaterally in the PVH of chloralose-anesthetized rabbits. Baseline blood pressure, HR, and LSNA did not change in response to the administration of lidocaine in the PVH. The magnitude of 'baroreflex responses' in HR and LSNA were expressed as the ratios of maximal changes in these parameters divided by the corresponding maximal changes in blood pressure. Application of lidocaine to the PVH produced a significantly greater decrease in LSNA (greater than 50%) compared to prelidocaine responses to baroreceptor stimulation. This increase in baroreflex response returned to the normal level during the recovery phase. In contrast, there was no significant change in the response of the HR to baroreceptor stimulation. Administration of norepinephrine into the PVH, intended to simulate possible changes in noradrenergic function, did not affect either LSNA or HR responses to baroreceptor stimulation. Interruption of neural activity in the PVH, augmented the inhibitory response of LSNA but not HR to baroreceptor stimulation. These results indicate that changes in peripheral sympathetic nerve activity and HR in response to baroreceptor activation may be affected differentially by specific forebrain structures such as PVH.     

Depression and immunity: A role for T cells?

Much attention has been paid to the potential role of the immune system in the pathophysiology of major depression in humans. While activation of innate immune responses currently dominates the research landscape, early studies in depressed patients demonstrating impairment in acquired immune responses, in particular T cell responses, may warrant further consideration. Intriguing data suggest that activated T cells may play an important neuroprotective role in the context of both stress and inflammation. For example, generation of autoreactive T cells through immunization with central nervous system (CNS) specific antigens has been shown to reverse stress-induced decreases in hippocampal neurogenesis as well as depressive-like behavior in rodents. In addition, trafficking of T cells to the brain following stress, in part related to glucocorticoids, has been found to reduce stress-induced anxiety-like behavior. Data indicate that T regulatory cells may also play a role in depression through downregulation of chronic inflammatory responses. Based on the notion that T cells may subserve neuroprotective and anti-inflammatory functions during stress and inflammation, impaired T cell function may directly contribute to the development of depression. Indeed, increased sensitivity to apoptosis as well as reduced responsiveness to glucocorticoids, may not only decrease the availability of T cells in depressed patients, but also may reduce their capacity to traffic to the brain in response to relevant neuroendocrine or immune stimuli. Further elucidation of T cell pathology may lead to new insights into immune system contributions to depression. Moreover, enhancement of T cell function may represent an alternative strategy to treat depression.