Extended exposure to sugar and/or caffeine produces distinct behavioral and neurochemical profiles in the orbitofrontal cortex of rats: Implications for neural function.

Caffeine is a psychostimulant commonly consumed with high levels of sugar. The increased availability of highly caffeinated, high sugar energy drinks could put some consumers at risk of being exposed to high doses of caffeine and sugar. Notably, research that has examined the consequences of this combination is limited. Here, we explored the effect of chronic exposure to caffeine and/or sugar on behavior and protein levels in the orbitofrontal cortex (OFC) of rats. The OFC brain region has been implicated in neuropsychiatric conditions, including obesity and addiction behaviors. Adult male Sprague-Dawley rats were treated for 26 days with control, caffeine (0.6 g/L), 10% sugar, or combination of both. Locomotor behavior was measured on the first and last day of treatment, then 1 week after treatment. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label-free quantitative shotgun analysis revealed that 21, 12, and 23% of proteins identified in the OFC were differentially expressed by sugar and/or caffeine. The results demonstrate that the intake of high levels of sugar and/or low to moderate levels of caffeine has different behavioral consequences. Moreover, each treatment results in a unique proteomic profile with different implications for neural health.

Quantitative shotgun proteomics reveals extensive changes to the proteome of the orbitofrontal cortex in rats that are hyperactive following withdrawal from a high sugar diet.

In most Westernized societies, there has been an alarming increase in the consumption of sugar-sweetened drinks. For many adults these drinks represent a substantial proportion of their total daily caloric intake. Here we investigated whether extended exposure to sugar changes behavior and protein expression in the orbitofrontal cortex (OFC). Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 10% sucrose solution. Locomotor behavior was measured on the first and last day of treatment, then 1 week after treatment. Following the 1-week period free from treatment, sucrose treated rats were significantly more active than the control. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free quantitative shotgun proteomic analyses of three rats from each group found 290 proteins were differentially expressed in the sucrose treated group when compared to the control group. Major changes in the proteome were seen in proteins related to energy metabolism, mitochondrial function and the cellular response to stress. This research does not seek to suggest that sugar will cause specific neurological disorders, however similar changes in proteins have been seen in neurological disorders such as Alzheimer's disease, Parkinson's disease and schizophrenia.

Quantitative Proteomic Analysis of the Orbital Frontal Cortex in Rats Following Extended Exposure to Caffeine Reveals Extensive Changes to Protein Expression: Implications for Neurological Disease.

Caffeine is a plant-derived psychostimulant and a common additive found in a wide range of foods and pharmaceuticals. The orbitofrontal cortex (OFC) is rapidly activated by flavours, integrates gustatory and olfactory information, and plays a critical role in decision-making, with dysfunction contributing to psychopathologies and neurodegenerative conditions. This study investigated whether long-term consumption of caffeine causes changes to behavior and protein expression in the OFC. Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 0.6 g/L caffeine solution. Locomotor behavior was measured on the first and last day of treatment, then again after 9 days treatment free following exposure to a mild stressor. When tested drug free, caffeine-treated animals were hyperactive compared to controls. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free shotgun proteomics found 157 proteins differentially expressed in the caffeine-drinking rats compared to control. Major proteomic effects were seen for cell-to-cell communication, cytoskeletal regulation, and mitochondrial function. Similar changes have been observed in neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia.

The relationship between neuropsychological functioning and FDG-PET hypometabolism in intractable mesial temporal lobe epilepsy.

We examined the relationship between baseline neuropsychological functioning and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in intractable mesial temporal lobe epilepsy (MTLE). We hypothesized relationships between dominant temporal lobe hypometabolism and verbal memory and between nondominant temporal lobe hypometabolism and nonverbal memory in line with the lateralized material-specific model of memory deficits in MTLE. We also hypothesized an association between performance on frontal lobe neuropsychological tests and prefrontal hypometabolism. Thirty-two patients who had undergone temporal lobectomy for treatment of MTLE and who completed both presurgical FDG-PET and comprehensive neuropsychological investigations with widely used standardized measures were included. Age-adjusted composite measures were calculated for verbal memory, nonverbal memory, relative material-specific memory, IQ, executive function, attention/working memory, and psychomotor speed. Fluorodeoxyglucose positron emission tomography was analyzed with statistical parametric mapping (SPM) to identify hypometabolism relative to healthy controls. Pearson's correlation was used to determine the relationship between regions of hypometabolism and neuropsychological functioning. Dominant temporal lobe hypometabolism was associated with relatively inferior verbal memory, while nondominant temporal lobe hypometabolism was associated with inferior nonverbal memory. No relationship was found between performance on any frontal lobe measures and prefrontal hypometabolism. Statistical parametric mapping-quantified lateralized temporal lobe hypometabolism correlates with material-specific episodic memory impairment in MTLE. In contrast, prefrontal hypometabolism is not associated with performance on frontal lobe measures. We suggest that this is because frontal lobe neuropsychology tests may not be good measures of isolated frontal lobe functioning.

The Effect of Eating Disorder Memoirs in Individuals With Self-Identified Eating Pathologies.

As part of a larger, mixed-methods study, we posted an invitation to participate in a study on the effects of reading eating disorder memoirs on the website of an organization that provides support for people with eating disorders. Twenty-four women completed the questionnaire. Qualitative analysis of their responses indicated a recovery continuum, whereby the direction of memoir influence seemed to depend on an individual's recovery stage and motivation to recover. Individuals who reported that they were exposed to memoirs before, or during, their illness reported experiencing negative consequences including making unfavorable social comparisons, along with emulation and triggering of disordered behaviors, whereas those who reported being exposed when in recovery reported more positive outcomes including hope, validation, and social support. Findings have implications for the use of personal accounts as a means of facilitating patient recovery in eating disorder treatment settings. Future research should test the influence of memoirs using a larger eating disorder sample, and across different recovery stages.

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy.

Religious and ethnic influences on willingness to donate organs and donor behavior: an Australian perspective.

CONTEXT: Globally, the demand for donated organs outstrips supply, meaning that there are both practical and theoretical reasons for examining factors that are predictive of individuals' willingness to donate their organs upon their death. OBJECTIVES: To determine whether individuals of different religious denominations living in Australia have different views on organ donation, whether donation attitudes differ significantly across ethnic groups, and whether factors identified in international research are predictors of willingness to donate and actual donor behavior in this population. PARTICIPANTS: Data for this study were collected from students at an Australian university from a range of religious and ethnic backgrounds, and their friends and relatives (N = 509). Intervention-Participants were administered the Organ Donation Attitude Scale, as well as additional attitudes and knowledge measures. MAIN OUTCOME MEASURES: Self-reported "willingness to donate" and "donor behavior". RESULTS: Our findings complemented those reported in comparable countries, with females, younger Australians, and those with high knowledge levels being more willing to donate than males, older persons, and those with low knowledge. Persons who described themselves as having stronger religious beliefs (particularly Buddhist and Islamic) held less favorable attitudes toward donation, had lower knowledge levels, and were more likely to oppose donation. CONCLUSIONS: Although this study established that attitudes toward, knowledge about, and predictors of organ donation in Australia are similar to those reported elsewhere, donation rates remain low. Further in-depth research examining the impact of religion and culture on attitudes, beliefs, and behavior is essential when exploring strategies to improve organ donation rates in highly multicultural societies such as Australia.

Attitudes toward organ donation and donor behavior: a review of the international literature.

OBJECTIVE: To conduct a systematic review of published research that assessed the predictors of attitudes toward deceased organ donation, willingness to donate, and donor behavior. DATA SOURCES: MEDLINE, PreMEDLINE, PsycInfo, and the Cumulative Index to Nursing and Allied Health Literature were searched for the period from 1988 to 2009. STUDY SELECTION: Eligible studies included members of the general public (i.e., not transplant recipients, donor families, or health professionals) and used multivariate analyses for quantitative assessment of predictors. Data Extraction-The search identified 33 relevant studies. Owing to heterogeneity in populations and measures, results were summarized rather than subjected to meta-analysis. DATA SYNTHESIS: Research suggests that individuals who are younger, female, have higher education levels and socioeconomic status, hold fewer religious beliefs, have high knowledge levels, know others with positive attitudes, are more altruistic, and have fewer concerns about manipulation of the body of the deceased donor are more likely to have positive attitudes toward donation and are more willing to donate their organs. CONCLUSIONS: The review revealed the complexity of individuals' attitudes toward donation and the need for more sophisticated future studies of the interactions between the broader factors influencing donation (such as social norms and existing legislation in each country) and individual factors, such as attitudes and beliefs. (Progress in Transplantation.

Re-evaluation of an animal model for ADHD using a free-operant choice task.

Previous research using free-operant procedures have reported that the Spontaneously Hypertensive Rat (SHR) is more impulsive and inattentive than the Wistar-Kyoto (WKY) rat. Recently these behavioural differences have been suggested to be a consequence of differences in the overall activity of these strains. This study compared SHRs to WKYs on locomotor activity and delay sensitivity using a delayed reinforcement (DR) and extinction (EXT) task. SHRs maintained higher locomotor activity than WKYs, however no significant group differences were found on the total lever presses in the DR or EXT tasks. During the DR task, SHRs shifted to selecting the immediate small reinforcer significantly faster than WKYs as the delay increased. WKYs predominantly selected the lever previously associated with the delayed large reinforcer throughout the EXT task, while the SHRs showed no such preference. The significant group differences found on lever selection during the DR and EXT tasks suggests that SHRs are more sensitive to delays, therefore providing further support for the face validity of the SHR as an animal model of ADHD.

A randomized controlled trial of a decision aid for women considering genetic testing for breast and ovarian cancer risk.

PURPOSE: To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. METHODS: A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post-consultation. RESULTS: While the DA had no effect on informed choice, post-decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). CONCLUSIONS: Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn.

A randomized trial of a breast/ovarian cancer genetic testing decision aid used as a communication aid during genetic counseling.

OBJECTIVES: To evaluate the impact of a decision aid for women considering genetic testing for breast/ovarian cancer risk given during genetic counseling. METHODS: One hundred and forty-eight women were randomized to receive the decision aid or a control pamphlet at the beginning of their first consultation with a genetic counselor. When the patient received the decision aid, it was used to complement consultation discussions about genetic testing. One hundred and ten (74.3%) women completed the first questionnaire designed to elicit information about women's levels of decisional conflict and knowledge about genetic testing. Of these, 105 (70.9%) completed a second questionnaire to assess longer-term outcomes, 6 months postconsultation. RESULTS: Results showed that women who received the decision aid felt more informed about genetic testing (chi(2)(1)=8.69; P=0.003), had clearer values (chi(2)(1)=6.90; P=0.009) and had higher knowledge levels (chi(2)(2)=6.49; P=0.039) than women who received the control pamphlet. CONCLUSIONS: The developed decision aid improved patient outcomes better than a control pamphlet when implemented during genetic counseling and given to the patient to take home.

Attitudes toward genetic testing for cancer risk after genetic counseling and decision support: a qualitative comparison between hereditary cancer types.

This study aimed to qualitatively assess individuals' attitudes toward genetic testing for cancer risk after genetic counseling and decision support. As part of a larger study, 78 women considering genetic testing for hereditary breast/ovarian cancer (HBOC) risk and 22 individuals considering genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) completed an open-ended table of their perceived pros and cons of genetic testing. The most frequently reported pros were "to help manage my risk of developing cancer," "to help my family," and "to know my cancer risk." With regards to risk management, the HBOC group perceived genetic testing as most helpful in informing their general risk management practices, while the HN-PCC group focused on the potential to clarify their need for bowel cancer screening, suggesting that patients' perceptions of the benefits of genetic testing may differ across cancer syndromes. Individuals in both groups expressed concern about the potential psychological impact of genetic testing. We also found that some affected individuals may not fully comprehend the meaning of their potential test results. Eliciting patients' perceived pros and cons during genetic counseling is likely to be a valuable tool for improving patient care. This data also provides an improved evidence base for the development of patient education tools.

Usefulness of the Threatening Medical Situations Inventory in individuals considering genetic testing for cancer risk.

OBJECTIVE: To assess the psychometric properties of the Threatening Medical Situations Inventory (TMSI) in a community sample (Study 1), and to examine its usefulness in individuals with a strong family history of cancer (Study 2). METHODS: Study 1 participants (N=276) completed 2 online surveys, 14 days apart. Study 2 participants (N=311) completed 2 questionnaires, 6 months apart. RESULTS: Both studies revealed the inventory was psychometrically sound, although some concerns were raised about the factor structure. High monitors in Study 1 reported desiring more health-related information and an active role in medical decision-making. High monitors in Study 2 had the greatest knowledge increase when they received a detailed decision aid, compared to a brief pamphlet. CONCLUSION: The TMSI is appropriate for use in both community and clinical samples. High monitors in the general community are more likely to prefer receiving as much health-related information as possible and desire an active role in decision-making about their health. PRACTICE IMPLICATIONS: Familial cancer clinic patients may benefit from tailoring the amount of information they receive to their coping style, such that patients who are vigilant information-seekers may benefit most from receiving more detailed information about genetic testing.

The behavioral effects of chronic sugar and/or caffeine consumption in adult and adolescent rats.

Caffeine is a psychostimulant frequently consumed by adults and children, often in combination with high levels of sugar. Chronic pretreatment with either substance can amplify both amphetamine and cocaine-induced hyperactivity in rodents. The present study sought to elucidate whether age at the time of exposure to sugar and/or caffeine alters sensitivity to an acute illicit psychostimulant (methamphetamine, [METH]) challenge in adulthood. Adult and adolescent (Postnatal Day 35 on first day of treatment) male Sprague-Dawley rats were treated for 26 days with water, caffeine (0.6 g/L), 10% sucrose or their combination. Locomotor behavior was measured on the first and last day of treatment. Following 9-days treatment free, animals were challenged with saline (1 ml/kg, i.p.) or METH (1 mg/kg, i.p.) and locomotor activity was measured. During the treatment period, adolescent rats maintained a higher caffeine (mg/kg) dose than their adult counterparts. Adding sugar to caffeine increased adolescent consumption and the highest caffeine dose consumed was measured in these animals. Drinking sugar-sweetened caffeinated water or combination did not produce cross-sensitization to METH administration in either age group. Nevertheless, the finding that regular exposure through adolescence to caffeinated sugar-sweetened beverages could increase consumption of caffeine and sugar later in life is important, as there is a large body of evidence that has linked excess consumption of sugar-sweetened beverages to a broad range of other negative physical and mental health outcomes. (PsycINFO Database Record

Methadone disrupts performance on the working memory version of the Morris water task.

The aim of the study was to examine if administration of the mu-opiate agonist methadone hydrochloride resulted in deficits in performance on the Morris water tank task, a widely used test of spatial cognition. To this end, after initial training on the task, Long-Evans rats were administered saline or methadone at either 1.25, 2.5 or 5 mg/kg ip 15 min prior to testing. The performance of the highest-dose methadone group was inferior to that of the controls on the working memory version of the Morris task. There were also differences between the groups on the reference memory version of the task, but this result cannot be considered reliable. These data show that methadone has its most profound effect on cognition in rats when efficient performance on the task requires attention to and retention of new information, in this case, the relationship between platform location and the extramaze cues.

Implicit and explicit olfactory memory in people with and without Down syndrome.

This study examined differences in implicit and explicit memory performance between people with Down syndrome (DS), their siblings, children matched on mental age, and university undergraduates, using olfactory stimuli. The DS and mental-age matched participants were also compared on two tasks of executive function. The data revealed implicit memory for olfactory stimuli. Further, people with DS performed similarly to each control group on the implicit memory task, but performed significantly poorer than all control groups on the explicit memory task. Impairment to executive functioning was identified as a possible cause of this deficit in explicit memory as people with DS performed more poorly than the mental-age matched controls on both tasks of executive function.

Long-term effects of chronic oral Ritalin administration on cognitive and neural development in adolescent wistar kyoto rats.

The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed "normal" (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in "normal" WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

Cerebellar dysfunction, cognitive flexibility and autistic traits in a non-clinical sample.

Cerebellar dysfunction and impaired cognitive flexibility are key features of autism spectrum disorders (ASD). However, despite the increasing interest in subclinical autism, no research has yet examined the relationship between these signs and autistic traits in the wider population. This study used the Autism-Spectrum Quotient (AQ) questionnaire to assess autistic traits in university students enrolled in either systems-oriented or humanities degree programmes. Participants also completed a battery of motor tasks designed to assess cerebellar function, and subscales from the Delis-Kaplan Executive Function System (D-KEFS) battery. Students enrolled in systems-oriented degrees had on average higher AQ scores than students enrolled in humanities degrees. The data showed a significant correlation between autistic traits and motor function scores, as well as between autistic traits and verbal set-shifting ability, as assessed on the D-KEFS. These data provide support for the autistic spectrum hypothesis, in indicating that key cognitive, neurological and behavioural features of autism carry over into non-clinical populations.

Validating the factor structure of the Self-Report Psychopathy scale in a community sample.

Currently, there is no standard self-report measure of psychopathy in community-dwelling samples that parallels the most commonly used measure of psychopathy in forensic and clinical samples, the Psychopathy Checklist. A promising instrument is the Self-Report Psychopathy scale (SRP), which was derived from the original version the Psychopathy Checklist. The most recent version of the SRP (SRP-III; D. L. Paulhus, C. S. Neumann, & R. D. Hare, in press) has shown good convergent and discriminate validity and a factor structure similar to the current version of the Psychopathy Checklist (PCL-R; R. D. Hare, 1991, 2003). The analyses in the current study further investigated the viability of the SRP-III as a PCL-R-analogous measure of psychopathy in nonforensic and nonclinical samples by extending the validation process to a community sample. Using confirmatory factor analyses and logistic regressions, the results revealed that a four-factor oblique model for the SRP-III was most tenable, congruent with the PCL-R factor structure of psychopathy and previous research in which the SRP-III was administered to a student sample.

Time perspective in hereditary cancer: psychometric properties of a short form of the Zimbardo Time Perspective Inventory in a community and clinical sample.

AIMS: We aimed to assess the psychometric properties of a 25-item short form of the Zimbardo Time Perspective Inventory in a community sample (N = 276) and in individuals with a strong family history of cancer, considering genetic testing for cancer risk (N = 338). RESULTS: In the community sample, individuals with high past-negative or present-fatalistic scores had higher levels of distress, as measured by depression, anxiety, and aggression. Similarly, in the patient sample, past-negative time perspective was positively correlated with distress, uncertainty, and postdecision regret when making a decision about genetic testing. Past-negative-oriented individuals were also more likely to be undecided about, or against, genetic testing. Hedonism was associated with being less likely to read the educational materials they received at their clinic, and fatalism was associated with having lower knowledge levels about genetic testing. CONCLUSIONS: The assessment of time perspective in individuals at increased risk of cancer can provide valuable clinical insights. However, further investigation of the psychometric properties of the short form of this scale is warranted, as it did not meet the currently accepted criteria for psychometric validation studies.