CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls.

The purpose of this study was to examine the differential effects of acute tryptophan (TRP) depletion vs. sham condition on plasma, cerebrospinal fluid (CSF) biochemical parameters, and mood in the following three subject groups: (1) nine antidepressant-free individuals with remitted depression, (2) eight paroxetine-treated individuals with recently remitted depression, and (3) seven healthy controls. Plasma TRP decreased during TRP depletion and increased during sham condition (p<.01). CSF TRP and 5-hydroxyindoleacetic acid were lower during TRP depletion than sham condition (p<.01 each). During TRP depletion, CSF TRP correlated significantly with the plasma sum of large neutral amino acids (SigmaLNAA) (R=-.52, p=.01), but did not significantly correlate with plasma TRP (R=.15, p=.52). The correlation between CSF TRP and ratio of TRP to SigmaLNAA was R=.41 and p=.06 during TRP depletion, and R=-.44 and p=.04 during sham condition. A negative correlation trend was observed between CSF-TRP levels and peak Hamilton Depression Rating Scale scores during TRP depletion in patients recovered from depression (R=-.45, p=.07), but not in healthy controls (R=-.01, p=.98). CSF neuropeptide Y was higher during TRP depletion than sham condition (t=1.75, p<.10). These results illustrate the importance of assessing plasma SigmaLNAA when using the TRP depletion paradigm. The use of a single CSF sampling technique although practical may result in data acquisition limitations.

Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders.

OBJECTIVE: The aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID). METHODS: Fourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and "optimal dose" for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) ADHD subscale of the Conners' Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD). RESULTS: MPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects. CONCLUSION: The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely.

Prospective, naturalistic, pilot study of open-label atomoxetine treatment in preschool children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to report preliminary data regarding effectiveness and tolerability of atomoxetine in 3- to 5-year-old preschool children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Nine boys and 3 girls (mean age = 5.0 +/- 0.72 years) diagnosed with ADHD were treated with atomoxetine in an open-label pilot study. Atomoxetine was gradually titrated to a maximum dose of 1.8 mg/kg per day. RESULTS: There was a significant effect of time from baseline to end point on the parent-rated hyperactivity/impulsivity Swanson Nolan and Pelham (SNAP-IV-HI) subscale ratings (F[9, 11] = 6.32, p < 0.0001). The mean difference between the baseline and end-point parent SNAP-IV-HI scores was 10.2 +/- 7.3 (p = 0.0005). The rate of positive response (defined as at least a 30% reduction in the end-point parent SNAP-IV-HI scores and a Clinical Global Impressions-Improvement [CGI-I] rating of Much Improved or Very Much Improved) was 75%. The Children's Global Assessment Scale scores improved significantly over time [F(9, 11) = 6.24 p < 0.001]. The mean end-point daily dose of atomoxetine was 1.59 +/- 0.3 mg/kg. A high proportion (66.7%) of the preschoolers experienced side effects with atomoxetine. Side effects of defiance, tantrums, aggression, and irritability were most disconcerting to parents, and gastrointestinal complaints were the most commonly reported adverse effects. One child was terminated from the study due to "chest ache." There were no changes in weight, height, or cardiovascular measures. CONCLUSION: This open-label pilot study provides preliminary evidence of effectiveness and tolerability of atomoxetine for treating ADHD in preschool children, although double-blind, randomized, placebo-controlled studies are needed to confirm this.

Age differences in recognition of emotion in lexical stimuli and facial expressions.

Age differences in emotion recognition from lexical stimuli and facial expressions were examined in a cross-sectional sample of adults aged 18 to 85 (N = 357). Emotion-specific response biases differed by age: Older adults were disproportionately more likely to incorrectly label lexical stimuli as happiness, sadness, and surprise and to incorrectly label facial stimuli as disgust and fear. After these biases were controlled, findings suggested that older adults were less accurate at identifying emotions than were young adults, but the pattern differed across emotions and task types. The lexical task showed stronger age differences than the facial task, and for lexical stimuli, age groups differed in accuracy for all emotional states except fear. For facial stimuli, in contrast, age groups differed only in accuracy for anger, disgust, fear, and happiness. Implications for age-related changes in different types of emotional processing are discussed.

Obstructive sleep apnea-hypopnea and neurocognitive functioning in the Sleep Heart Health Study.

BACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea (OSAH) is associated with sleep fragmentation and nocturnal hypoxemia. In clinical samples, patients with OSAH frequently are found to have deficits in neuropsychological function. However, the nature and severity of these abnormalities in non-clinical populations is less well defined. PATIENTS AND METHODS: One hundred and forty-one participants from the Tucson, AZ and New York, NY field centers of the Sleep Heart Health Study completed a battery of neuropsychological tests for 9-40 months (mean=24 months, SD=7 months) after an unattended home polysomnogram. Sixty-seven participants had OSAH (AHI>10) and 74 did not have OSAH (control (CTL), apnea-hypopnea index (AHI)<5). In addition to the individual tests, composite variables representing attention, executive function, MotorSpeed and processing speed were constructed from the neuropsychological test battery. RESULTS: There were no significant differences in any individual neuropsychological test or composite variable between the OSAH and CTL groups. However, when time spent with O(2) saturations less than 85% was dichotomized into those participants in the top quartile of the distribution and those in the lower three quartiles, motor speed was significantly impaired in those who were more hypoxemic. In addition, poorer motor speed (model adjusted R(2)=0.242, P<0.001) and processing speed performance (model adjusted R(2)=0.122, P<0.001) were associated with more severe oxygen desaturation even after controlling for degree of daytime sleepiness, age, gender and educational level. CONCLUSIONS: Mild to moderate OSAH has little impact on the selected measures of attention, executive function, motor speed and processing speed. However, hypoxemia adversely affects both motor and processing speed. These results suggest that in middle-aged to elderly adults the neuropsychological effects of clinically unrecognized mild to moderate OSAH are neither global nor large.

Postpartum depression assessments at well-baby visits: screening feasibility, prevalence, and risk factors.

BACKGROUND: Postpartum depression (PPD) is a disorder with broad public health implications and consequences that impact almost every aspect of child development. METHODS: In this pilot study, study participants were 96 women who brought their babies to the University of Arizona Pediatrics Clinic for their 8-week well-baby visit. Participants completed a packet that consisted of questions about demographics, potential correlates of PPD, and the Edinburgh Postpartum Depression Scale (EPDS). English and Spanish versions were available. RESULTS: Of a total of 172 women who brought their babies in for their 8-week well-baby visit, 96 women completed the packets, for an overall response rate of 56.9%. Observed EPDS scores ranged from 0 to 18, with a mean of 5.44 and a standard deviation (SD) of 4.83. Using the cutoff of EPDS > or = 12, 14.6% of participants were likely suffering from clinically significant depression. Higher EPDS scores and also categorical depression classification were statistically associated with reported smoking and a family history of mental health problems. CONCLUSIONS: We conclude that screening for mothers at well-baby visits is feasible and that the data collected are of sufficient quality to identify reliable predictors even with small sample sizes.

Forward association, backward association, and the false-memory illusion.

In the Deese-Roediger-McDermott false-memory illusion, forward associative strength (FAS) is unrelated to the strength of the illusion; this is puzzling, because high-FAS lists ought to share more semantic features with critical unpresented words than should low-FAS lists. The authors show that this null result is probably a truncated range artifact. When FAS and its complement, backward associative strength (BAS), were independently manipulated in factorial designs, they both affected illusion strength. Moreover, their effects did not interact and were of comparable magnitude. Conjoint-recognition analyses were used to pinpoint the influence of BAS and FAS on retrieval processes that support or suppress false-memory responses. Although the variables affected both types of processes, their effects on suppressive processes were larger and more consistent. This research also provided the first clear evidence that subjects often use suppressive processes inappropriately to reject studied items that preserve the gist of experience.

Recollection rejection: false-memory editing in children and adults.

Mechanisms for editing false events out of memory reports have fundamental implications for theories of false memory and for best practice in applied domains in which false reports must be minimized (e.g., forensic psychological interviews, sworn testimony). A mechanism posited in fuzzy-trace theory, recollection rejection, is considered. A process analysis of false-memory editing is presented, which assumes that false-but-gist-consistent events (e.g., the word SOFA, when the word COUCH was experienced) sometimes cue the retrieval of verbatim traces of the corresponding true events (COUCH), generating mismatches that counteract the high familiarity of false-but-gist-consistent events. Empirical support comes from 2 qualitative phenomena: recollective suppression of semantic false memory and inverted-U relations between retrieval time and semantic false memory. Further support comes from 2 quantitative methodologies: conjoint recognition and receiver operating characteristics. The analysis also predicts a novel false-memory phenomenon (erroneous recollection rejection), in which true events are inappropriately edited out of memory reports.

The impact of reproductive events on the course of bipolar disorder in women.

BACKGROUND: Little is known about the impact of female reproductive hormones on the course of bipolar disorder. This study was designed to assess the influence of reproductive events and hormonal therapies on the course of bipolar disorder in women. METHOD: Fifty women with DSM-IV bipolar disorder completed a structured clinical interview to assess the impact of reproductive events on the course of their illness. RESULTS: The onset of bipolar disorder occurred before menarche in 32% (N = 16) of women; 18% (N = 9) experienced the onset within 1 year of menarche. Most women did not receive an accurate diagnosis of nor treatment for bipolar disorder until after they had children, and therefore the majority were not treated with mood stabilizers during or immediately after pregnancies. Of women with children, 20 (67%) of 30 experienced a postpartum mood episode. Of the women who had postpartum episodes after delivery of a first child, all had episodes after subsequent pregnancies. Having a postpartum mood episode after a first pregnancy significantly increased the risk of a postpartum episode after subsequent deliveries (p = .02). Postpartum episodes were almost exclusively depressive. Increased depressive symptoms during pregnancy were significantly associated with postpartum mood episodes (p = .01). Women who were not using hormone replacement therapy (HRT) were significantly more likely than those who were using HRT to report worsening of symptoms during perimenopause/menopause (p = .02). CONCLUSION: These data suggest that hormonal fluctuations are associated with increased risk of affective dysregulation and mood episodes in women with bipolar disorder.