Longitudinal study of striatal activation to reward and loss anticipation from mid-adolescence into late adolescence/early adulthood.

Adolescent risk-taking behavior has been associated with age-related changes in striatal activation to incentives. Previous cross-sectional studies have shown both increased and decreased striatal activation to incentives for adolescents compared to adults. The monetary incentive delay (MID) task, designed to assess functional brain activation in anticipation of reward, has been used extensively to examine striatal activation in both adult and adolescent populations. The current study used this task with a longitudinal approach across mid-adolescence and late adolescence/early adulthood. Twenty-two participants (13 male) were studied using the MID task at two time-points, once in mid-adolescence (mean age=16.11; SD=1.44) and a second time in late adolescence/early adulthood (mean age=20.14; SD=.67). Results revealed greater striatal activation with increased age in high- compared to low-incentive contexts (incentive magnitude), for gain as well as for loss trials (incentive valence). Results extend cross-sectional findings and show reduced striatal engagement in adolescence compared to adulthood during preparation for action in an incentive context.

Baseline cerebral hypermetabolism associated with carbamazepine response, and hypometabolism with nimodipine response in mood disorders.

BACKGROUND: Positron emission tomography (PET) studies have reported baseline (medication free) differences between mood disorder patients and healthy control subjects, but relatively little is known about relationships between baseline PET scans and treatment responses. Carbamazepine (CBZ) and to a more limited extent nimodipine (NIMO) seem useful in mood disorders. We explored whether baseline regional cerebral glucose metabolism (rCMRglu) could discriminate CBZ and NIMO responders from nonresponders and healthy control subjects. METHODS: In refractory mood disorder patients, we examined relationships between responses to these drugs, assessed by Clinical Global Impression-Improvement scores, and baseline rCMRglu, determined with fluorine-18 deoxy-glucose and PET. RESULTS: CBZ responders had baseline left insular hyper-metabolism compared to healthy control subjects and nonresponders, whereas nonresponders had widespread (including left insular) hypometabolism. Degree of CBZ response correlated with baseline paralimbic (including insula) and prefrontal hypermetabolism. In responders but not nonresponders, CBZ decreased widespread metabolism, with the degree of decrease in left insula correlating with response. In contrast, NIMO responders but not nonresponders had baseline widespread (including left insular) hypometabolism. Left prefrontal and left insular baseline hypometabolism, but not metabolic changes with treatment correlated with degree of NIMO response. CONCLUSIONS: These data suggest that baseline anterior paralimbic and prefrontal hypermetabolism may be associated with CBZ response, and hypometabolism with NIMO response. Based on these preliminary data, further exploration of relationships between baseline PET scans and treatment responses is indicated.

Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients.

BACKGROUND: We studied the relationship between regional cerebral metabolism and the severity of anxiety in mood disorder patients, controlling for depression severity. METHODS: Fifty-two medication-free patients with unipolar or bipolar illness underwent positron emission tomography with [(18)F]-fluorodeoxyglucose. Hamilton Depression Rating Scale and Spielberger Anxiety-State Scale scores were obtained for the week of the scan. Analyses were performed on globally normalized images and were corrected for multiple comparisons. RESULTS: After covarying for depression scores, age, and gender, Spielberger Anxiety-State Scale scores correlated directly with regional cerebral metabolism in the right parahippocampal and left anterior cingulate regions, and inversely with metabolism in the cerebellum, left fusiform, left superior temporal, left angular gyrus, and left insula. In contrast, covarying for anxiety scores, age, and gender, Hamilton Depression Rating Scale scores correlated directly with regional cerebral metabolism in the bilateral medial frontal, right anterior cingulate, and right dorsolateral prefrontal cortices. CONCLUSIONS: Comorbid anxiety symptoms are associated with specific cerebral metabolic correlates that partially overlap with those in the primary anxiety disorders and differ from those associated with depression severity.

Regional brain activity during transient self-induced anxiety and anger in healthy adults.

BACKGROUND: Several studies have demonstrated that transient self-induced sadness activates anterior paralimbic structures. To further examine the specificity of these findings and the neural substrates involved in anger and anxiety, we studied the neural correlates of the induction of anxiety and anger in healthy adults. METHODS: We used H2(15)O and positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in 16 healthy adults during the induction of transient anxiety, anger, and neutral emotions. Subjects achieved differential emotions by recalling prior life events while viewing affect-appropriate faces. RESULTS: Both the anxiety and anger conditions were associated with increased normalized rCBF in left inferior frontal and left temporal pole regions and decreased rCBF in right posterior temporal/parietal and right superior frontal cortex, compared to the neutral induction. Additionally, compared to neutral induction, anxiety was associated with increased rCBF in the left anterior cingulate and cuneus and decreased rCBF in right medial frontal cortex, while the anger induction was uniquely associated with increased rCBF in right temporal pole and thalamus. CONCLUSIONS: Self-generated transient states of anxiety and anger are associated with both overlapping and distinct regional brain activity patterns and provide a template for further dissection of specific components of normal and pathologic emotions.

Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder.

BACKGROUND: Functional brain imaging studies in unipolar and secondary depression have generally found decreased prefrontal cortical activity, but in bipolar disorders findings have been more variable. METHODS: Forty-three medication-free, treatment-resistant, predominantly rapid-cycling bipolar disorder patients and 43 age- and gender-matched healthy control subjects had cerebral glucose metabolism assessed using positron emission tomography and fluorine-18-deoxyglucose. RESULTS: Depressed bipolar disorder patients compared to control subjects had decreased global, absolute prefrontal and anterior paralimbic cortical, and increased normalized subcortical (ventral striatum, thalamus, right amygdala) metabolism. Degree of depression correlated negatively with absolute prefrontal and paralimbic cortical, and positively with normalized anterior paralimbic subcortical metabolism. Increased normalized cerebello-posterior cortical metabolism was seen in all patient subgroups compared to control subjects, independent of mood state, disorder subtype, or cycle frequency. CONCLUSIONS: In bipolar depression, we observed a pattern of prefrontal hypometabolism, consistent with observations in primary unipolar and secondary depression, suggesting this is part of a common neural substrate for depression independent of etiology. In contrast, the cerebello-posterior cortical normalized hypermetabolism seen in all bipolar subgroups (including euthymic) suggests a possible congenital or acquired trait abnormality. The degree to which these findings in treatment-resistant, predominantly rapid-cycling patients pertain to community samples remains to be established.

Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism.

BACKGROUND: Recent studies suggest that both high frequency (10-20 Hz) and low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) have an antidepressant effect in some individuals. Electrophysiologic data indicate that high frequency rTMS enhances neuronal firing efficacy and that low frequency rTMS has the opposite effect. METHODS: We investigated the antidepressant effects of 10 daily left prefrontal 1 Hz versus 20 Hz rTMS with the hypothesis that within a given subject, antidepressant response would differ by frequency and vary as a function of baseline cerebral glucose metabolism. After baseline PET scans utilizing [18F]-Fluorodeoxyglucose, thirteen subjects participated in a randomized crossover trial of 2 weeks of 20 Hz paired with 2 weeks 1 Hz or placebo rTMS. RESULTS: We found a negative correlation between degree of antidepressant response after 1 Hz compared to 20 Hz rTMS (r = -0.797, p < .004). Additionally, better response to 20 Hz was associated with the degree of baseline hypometabolism, whereas response to 1 Hz rTMS tended to be associated with baseline hypermetabolism. CONCLUSIONS: These preliminary results suggest that antidepressant response to rTMS might vary as a function of stimulation frequency and may depend on pretreatment cerebral metabolism. Further studies combining rTMS and functional neuroimaging are needed.

Chlorine inhalation toxicity from vapors generated by swimming pool chlorinator tablets.

We have presented two cases of serious respiratory injury after brief exposure to vapors from solid chlorine compounds. We could find no previous reports of such accidents and, therefore, have related these cases to alert the medical community. We would recommend that physicians caring for children include warnings about these preparations in their routine counseling of parents.

Warning labels. A source of toxicity information for parents.

The Hazardous Substances Act specifies that warning labels for household products contain specific signal words. This study was designed to determine whether this warning label format provides enough information for parents to accurately assess product toxicity. One hundred forty-two parents from two different sites (community health clinic, private pediatrician's office) were asked to rate the toxicity of four common household products (Crystal Drano, Lysol Basin/Tub and Tile Cleaner, Clorox Bleach, Tempera Poster Paint) and four imaginary products based on the warning labels found on them. Parents had a fairly accurate perception of the toxicity of products and the toxicity to be anticipated based on the warning label. There was considerable variability in response for products which were less toxic or nontoxic. Confusion was noted regarding the meaning of the term nontoxic.

Position paper update: ipecac syrup for gastrointestinal decontamination.

CONTEXT: An update of the first position paper on ipecac syrup from 1997 was published by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data. METHODS: A systematic review of the literature from the year 2003 forward. RESULTS: The literature search yielded a limited number of meaningful articles, and there remains no convincing evidence from clinical studies that ipecac improves the outcome of poisoned patients. Furthermore, the availability of ipecac is rapidly diminishing. CONCLUSIONS: The routine administration of ipecac at the site of ingestion or in the emergency department should definitely be avoided. Ipecac may delay the administration or reduce the effectiveness of activated charcoal, oral antidotes, and whole bowel irrigation. There is not sufficient evidence to warrant any change in the previous ipecac position papers. There are, however, insufficient data to support or exclude ipecac administration soon after ingestion of some specific poisons in rare situations.

Position paper update: gastric lavage for gastrointestinal decontamination.

CONTEXT: The first update of the 1997 gastric lavage position paper was published by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists in 2004. This second update summarizes the 2004 content and reviews new data. METHODS: A systematic review of the literature from January 2003 to March 2011 yielded few studies directly addressing the utility of gastric lavage in the treatment of poisoned patients. RESULTS: Sixty-nine new papers were reviewed. Recent publications continue to show that gastric lavage may be associated with serious complications. A few clinical studies have recently been published showing beneficial outcomes, however, all have significant methodological flaws. CONCLUSIONS: At present there is no evidence showing that gastric lavage should be used routinely in the management of poisonings. Further, the evidence supporting gastric lavage as a beneficial treatment in special situations is weak, as is the evidence to exclude benefit in all cases. Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients. In the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise.

Opposite effects of high and low frequency rTMS on mood in depressed patients: relationship to baseline cerebral activity on PET.

BACKGROUND: Optimal parameters of rTMS for antidepressant efficacy in general, or within patients, have not been adequately delineated. METHODS: Using a double-blind, sham-controlled, cross-over design, 22 adult patients with treatment refractory major depression (n=9; bipolar disorder, depressed phase) were randomized to active rTMS (20-Hz or 1-Hz) or sham rTMS conditions and given 5 rTMS treatments per week for two weeks. Repetitive TMS was administered at 100% of motor threshold for 1600 pulses over the left prefrontal cortex using a figure-eight coil. Patients initially randomized to sham rTMS were then exposed to two weeks of active rTMS with each frequency under blinded conditions. Those who received active 20-Hz and 1-Hz rTMS were crossed over to the opposite frequency for two weeks. Improvement in Hamilton Depression ratings were assessed after each two-week treatment phase. PET imaging was used to evaluate the patient's baseline absolute regional cerebral activity (blood flow and metabolism) as potential predictor of clinical response. RESULTS: Changes in depression severity on 1-Hz and 20-Hz rTMS were inversely correlated. PET scans with baseline hypoperfusion (but not hypometabolism) were associated with better improvement on 20-Hz rTMS as predicted. LIMITATIONS: The magnitude of the clinical change with either frequency at 100% motor threshold was not robust, and larger studies with higher intensities of rTMS for longer durations of time should be explored. CONCLUSIONS: High and low frequency rTMS exerts differential effects on depressed mood within individual subjects. The brain activity predictors and correlates of an optimal antidepressant response to rTMS remain to be better defined.

Pharmacists' poison prevention advice to the elderly.

Up to 36% of childhood ingestions take place in grandparents' homes. We surveyed the 1544 registered pharmacists in the state of Nebraska by a mailed anonymous questionnaire concerning their poison prevention practices with the elderly. Of the 26% respondents, 75% always or usually gave older adults a choice of child-resistant containers but estimated that 65% chose non-child-resistant containers. Fifty-two percent reported that they asked older adults about children who could possibly ingest medications, and 59% reported that they had poison prevention material available. However, over 50% of pharmacists reported that they neither actively counseled nor handed out poison prevention material to the elderly, and only 9% reported that they specifically advise older adults about poison prevention. If all pharmacists targeted poison control education to the elderly, childhood poisoning by drugs could be reduced by one-third.

A severe organophosphate poisoning requiring the use of an atropine drip.

A 68-year-old male attempted suicide by drinking three ounces of concentrated Cygon 2-E (23.4% dimethoate). He was immediately brought to the hospital, responded to standard treatment (ipecac, activated charcoal, 2-PAM, atropine), and was transferred from the ICU to general care 24 hours after the exposure. Within eight hours of the transfer, he relapsed and was moved to the CCU, where he required five milligrams of atropine every ten minutes for 24 hours, before being started on an atropine drip. The patient was maintained on the atropine drip (0.5-2.4 mg/kg/hr) for five weeks. He required a total atropine dose of 30 grams, the largest amount ever reported to have been administered to a human. Although S-ChE activities gradually increased they were not found to be helpful in determining when the drip could be safely stopped. Control of hypersecretions served as the best monitoring parameter for titration of the drip rate. The patient recovered completely with the exception of a detectable sensorineural hearing deficit, a slight, nonspecific personality change, and minimal spastic rigidity thought to be secondary to several anoxic episodes.

A survey of the expectations of New Mexico emergency physicians regarding the services of the New Mexico Poison and Drug Information Center.

OBJECTIVE: Physicians have been surveyed concerning their satisfaction with poison center services but have never been questioned regarding their expectations. This study was conducted to clarify the expectations of emergency physicians in New Mexico regarding the service of their regional poison center, the New Mexico Poison and Drug Information Center. DESIGN: Five New Mexico emergency department physicians were interviewed about their expectations when calling the New Mexico Poison and Drug Information Center. Their responses were combined with unique, additional expectations identified by the New Mexico Poison and Drug Information Center staff in order to develop a 62-item physician expectation mail survey instrument. Respondents were asked to rank the importance of each service expectation on a 5-point Likert scale (1 = not important, 5 = extremely important). RESULTS: A usable return rate of 60% was achieved (104 surveys). Fifty-eight (94%) expectations had a mean importance rating of > or = 3 (important). Ninety-four percent of the expectations included on the survey were being provided by the New Mexico Poison and Drug Information Center. CONCLUSION: Currently, there is a good fit between New Mexico emergency physician expectations and New Mexico Poison and Drug Information Center services provided. The instrument identified several areas where service was expected but not provided (Internet access to poison center, provision of industrial/occupational toxicology services, provision of tele-medicine capability) and where service was provided but not expected (drug dosing information). Surveying can be a valuable tool for clarifying expectations for poison center services.

Butoxyethanol ingestion with prolonged hyperchloremic metabolic acidosis treated with ethanol therapy.

BACKGROUND: Severe toxic ingestions of butoxyethanol (CAS No. 111-76-2) are rare despite the prevalence of this glycol ether in products such as glass and surface cleaners. Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases. Furthermore, the optimal therapeutic approach is not yet established. Much of the toxicity of butoxyethanol has been ascribed to its aldehyde and acid metabolites which are similar to those produced by oxidative metabolism of methanol and ethylene glycol. Although the roles of alcohol dehydrogenase inhibition with ethanol or fomepizole and hemodialysis are clear in the case of toxic ingestions of methanol and ethylene glycol, they remain poorly defined for butoxyethanol poisoning. CASE REPORT: We report the case of a 51-year-old female who ingested up to 8 ounces of Sanford Expo White Board Cleaner (butoxyethanol and isopropanol). She developed prolonged hyperchloremic metabolic acidosis and mental status depression and was treated with ethanol therapy but not hemodialysis. This patient recovered without apparent sequelae. The kinetics of butoxyethanol metabolism in this case are described and the potential therapeutic options are discussed.

Rapid onset: a valid panic disorder criterion?

This study examined the value of the DSM-IV time criterion for panic disorder (PD) requiring an abrupt onset to panic attacks (PAs) with a time to peak intensity (TTPI) of less than 10 min, and evaluated features distinguishing rapid onset (TTPI < 10) from prolonged onset (TTPI > 10) panickers. Eight hundred and sixty-four respondents to the National Institute of Mental Health Panic Disorder Questionnaire (NIMH PQ) who met the first three PD criteria were compared based on the time criterion. The prolonged onset panickers (18.2%) did not differ significantly from rapid onset panickers (81.8%) on any of 100 items assessing clinical symptoms, course of illness, and comorbidity of PD. These results suggest that many patients with otherwise classic features of PD have a prolonged TTPI of PAs, and that patients with prolonged-onset PAs are similar to patients with rapid-onset PAs on most measures. The reliability, validity, and clinical relevance of the current DSM-IV TTPI criterion should be evaluated in future studies.

Continuous naloxone infusion in pediatric narcotic overdose.

A 31-month-old girl required constant intravenous (IV) infusion of naloxone hydrochloride to treat codeine-induced respiratory and CNS depression. The infusion rate was 0.4 mg/hr (27 micrograms/kg/hr) over nine hours, without apparent side effects or evidence of toxic effects, for a total naloxone hydrochloride dose of 4.1 mg (280 micrograms/kg). Constant naloxone hydrochloride infusion at an initial rate of 0.4 mg/hr in pediatric narcotic poisoning should be considered if the patient responds inadequately to an initial 0.01-mg/kg bolus, requires repeated administration to reverse narcotic-induced effects, or has ingested long-acting agents. Continuous IV naloxone infusion is a convenient, safe, and effective method to treat narcotic overdose.

Toxicities and outcomes associated with nefazodone poisoning: an analysis of 1,338 exposures.

Toxicities and medical outcomes associated with nefazodone poisoning were characterized using national poisoning data from the American Association of Poison Control Centers and through prospective collection of additional data elements. Nefazodone exposures involving concomitant agents were excluded. There were 1,338 human exposures included in the final data analysis. Seventy-five percent of exposures were acute and 20% involved children < 13 years. Twenty-five percent of patients remained asymptomatic. There were no deaths. No dose response relationship was evident in the 45 cases where estimated doses were available. The most common manifestations were drowsiness (17.3% of all patients), nausea (9.7%), and dizziness (9.5%). The most common serious clinical effect was hypotension (1.6%). The median onset time for symptoms was 1.75 hours. Manifestations resolved within 8 to 24 hours. Most patients were treated with only gastrointestinal decontamination. No patients required intubation, mechanical ventilation, or vasopressors. Nefazodone appears to be of low toxicity during poisonings.