Self-critical perfectionism and depression maintenance over one year: The moderating roles of daily stress-sadness reactivity and the cortisol awakening response.

This study of depressed outpatients (N = 43) examined daily stress-sadness reactivity and the cortisol awakening response (CAR) as moderators of the relationship between self-critical (SC) perfectionism and depression over one year. Participants completed perfectionism measures at baseline (Time 1), daily diaries and salivary sampling six months later (Time 2), and an interviewer-rated depression measure at Time 1, Time 2, and one year after baseline (Time 3). Hierarchical multiple regression analyses of moderator effects demonstrated that patients with higher SC perfectionism and higher levels of daily stress-sadness reactivity (i.e., greater increases in daily sadness in response to increases in daily stress) had less improvement in depressive symptoms at Time 3 relative to those of other patients, adjusting for the effects of Time 1 and Time 2 depression. Furthermore, higher SC perfectionism in conjunction with an elevated CAR predicted higher levels of depression at Time 3. In addition, lower SC perfectionism in combination with higher levels of stress-sadness reactivity/CAR was associated with the lowest levels of depression at Time 3. These findings highlight the importance of targeting dysfunctional self-critical characteristics that exacerbate the impact of heightened stress-sadness reactivity and CAR to generate better treatment outcomes for patients with higher SC perfectionism. (PsycINFO Database Record

Nocturnal polysomnographic sleep across the menstrual cycle in premenstrual dysphoric disorder.

OBJECTIVES: Women with premenstrual dysphoric disorder (PMDD) experience disturbed mood, altered melatonin circadian rhythms, and frequent reports of insomnia during the luteal phase (LP) of their menstrual cycle. In this study we aimed to investigate nocturnal polysomnographic (PSG) sleep across the menstrual cycle in PMDD women and controls. METHODS: Seven PMDD women who indicated insomnia during LP, and five controls, spent every third night throughout a complete menstrual cycle sleeping in the laboratory. RESULTS: In PMDD and controls progesterone and core body temperature (BT(core)) were elevated during LP compared to the follicular phase (FP). Stage 2 sleep showed a significant main effect of menstrual phase and was significantly increased during mid-LP compared to early-FP in both groups. Rapid eye movement (REM) sleep for both groups was decreased during early-LP compared to early-FP. Slow wave sleep (SWS) was significantly increased, and melatonin significantly decreased, in PMDD women compared to controls. CONCLUSIONS: PMDD women who experience insomnia during LP had decreased melatonin secretion and increased SWS compared to controls. The sleep and melatonin findings in PMDD women may be functionally linked. Results also suggest an altered homeostatic regulation of the sleep-wake cycle in PMDD, perhaps implicating melatonin in the homeostatic process of sleep-wake regulation.

Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms.

INTRODUCTION: Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. METHOD: Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. RESULTS: Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. CONCLUSIONS: Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations.

Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.

Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

Are biomarkers of chronic alcohol misuse useful in the assessment of DWI recidivism status?

UNLABELLED: A first driving while impaired by alcohol (DWI) conviction is a key opportunity to identify offenders who are at high risk for recidivism. Detection of alcohol use disorder (AUD) is a major target of current DWI assessments. However, offenders frequently underreport their alcohol consumption, and use of biomarkers has been proposed as a more objective indicator. Among the best established are aspartate aminotranferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), mean corpuscular red blood cell volume (MCV), carbohydrate-deficient transferrin (CDT), and thiamine. To our knowledge, no research has directly verified whether AUD biomarkers predict DWI recidivism status. Using a cross-sectional design, this study tested three hypotheses related to the utility of biomarkers in DWI assessment. HYPOTHESES: (1) DWI recidivists possess biomarkers indicative of greater prevalence of AUD compared to first-time offenders; (2) multiple biomarkers better differentiate first-time offenders from recidivists compared to individual biomarkers; and (3) biomarkers add significantly to the prediction of recidivism over and above psychosocial questionnaires. METHODS: First-time offenders (n = 49) and recidivists (n = 95) participated in the study. In addition to self-reported information on sociodemographic and driving characteristics, data from several AUD questionnaires were gathered: Michigan Alcoholism Screening Test, Alcohol Use Disorders Identification Test, Composite International Diagnostic Interview, and Timeline Follow-Back. Blood samples were collected to measure AST, ALT, GGT, MCV, CDT, and thiamine. RESULTS: AUD biomarkers, taken individually or in combination, did not indicate that recidivists had more frequent AUD compared to first-time offenders. Also, they failed to significantly differentiate first-time offenders from recidivists or predict recidivism status. Finally, the superiority of biomarkers over psychosocial AUD questionnaires was not supported in the laboratory setting. CONCLUSION: The present findings suggest that biomarkers of chronic patterns of heavy drinking may not be adequate to capture the multiple processes that appear to promote recidivism (e.g., binge drinking, other risky behavioural and personality features). Despite their objectivity, caution is warranted in the interpretation of a positive score on these biomarkers in DWI assessment. Longitudinal research is needed to more comprehensively explore the relationship between positive biomarkers in first-time offenders and their risk of becoming recidivists.

Induction of tolerance of dopaminergic responses in man.

Schizophrenia may reflect a sensitization of dopaminergic (DA) function. Apomorphine (Apo), a DA receptor agonist, induces both sensitization and tolerance of DA function in rodents depending on dose intervals. We investigated sensitization and tolerance to Apo in healthy male volunteers. After a period of acclimatization to the experimental setting (Day 1) subjects were assigned randomly to two groups: Group A subjects received seven injections of placebo (physiological saline) (PLA) and Group B subjects received seven injections of Apo HCl (7 microg/kg sc) under double-blind conditions at 2 h intervals commencing at 0930 hours (Day 2) after an overnight fast. Twelve hours after the seventh injection, i.e. on Day 3, after an overnight fast all subjects received an injection of Apo. Serial samples of blood commencing at 0900 hours were drawn after the first and last injection in both groups for assay of growth hormone (GH), prolactin (PRL) and cortisol by radioimmunoassay; sleepiness was measured using the Analog Sleepiness Rating Scale and yawning recorded by video recorder. The GH response in Group B (N = 8) was (a) decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.03) and (b) decreased after the eighth injection of Apo compared with the first injection of Apo in Group A (N = 10) (P = 0.001). The number of yawns in Group B was significantly decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.042). PRL, cortisol and sleepiness were not significantly different between the first and eighth injection of Apo. Sensitization was not observed in any of the measures studied. These results are compatible with induction of acute tolerance of DA-mediated GH and yawning responses. The method used provides a safe pharmacological paradigm to examine plasticity of DA mechanisms in man. Results are discussed in the context of possible therapeutic implications for schizophrenia.

Dissocial behavior, the 5HTTLPR polymorphism, and maltreatment in women with bulimic syndromes.

We recently reported that, among bulimic women, previously abused carriers of the 5HTTLPR S allele showed special propensities towards novelty seeking (implying recklessness or impulsivity) and interpersonal insecurity. We subsequently re-analyzed our data, to examine the bearing of the 5HTTLPR polymorphism and prior sexual or physical maltreatment upon validated, higher-order personality-traits. Ninety women with bulimic syndromes were genotyped for 5HTTLPR "short" (S) and "long" (L(G) and L(A)) alleles, and then assessed for eating symptoms, history of sexual or physical abuse, and the higher-order personality traits Emotional Dysregulation, Dissocial Behavior, Inhibition, and Compulsivity. With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least one S-allele copy), multiple regression indicated a significant proportion of variance in Dissocial Behavior to be explained by an abuse x genotype interaction-greater psychopathology occurring in abused S-allele carriers. A parallel analysis applying a triallelic model of 5HTTLPR (i.e., presence or absence of at least one copy of presumably low-function S or L(G) alleles) produced a similar pattern, but no statistically significant effect. The finding that bulimic 5HTTLPR S-allele carriers who are previously abused display elevations on Dissocial Behavior corroborates previous observations concerning phenomenological correlates of traumatic stress in 5HTTLPR S allele carriers. (c) 2007 Wiley-Liss, Inc.

Neurocognitive characteristics of DUI recidivists.

Individuals who drive under the influence (DUI) of alcohol may be at greater risk for neurocognitive impairment because of their exposure to multiple sources of neurological risk. This could contribute to the persistence of DUI behaviour and influence the effectiveness of remedial interventions. The objectives of this study were to clarify the neurocognitive characteristics of DUI recidivists and the nature of potential impairments, and to explore relationships between these characteristics and the frequency of past DUI convictions. One hundred male recidivists were evaluated for visuospatial constructional abilities and visual memory, verbal fluency, attention skills, cognitive flexibility, spatial planning, and verbal and movement inhibition. Results indicated that a majority of recidivists showed signs of neurocognitive impairment on several dimensions. Impairment was most marked on visuospatial constructional abilities and visual memory. In contrast to previous studies, no participants were found to have impulse control problems. Measures of memory and cognitive efficiency were significantly associated with the frequency of past convictions. Finally, exploratory analyses of two potential sources of impairment, alcohol exposure and head trauma, suggested the role of excessive alcohol use as the most obvious associated factor. Overall, the findings indicate that neurocognitive impairments are a common feature in recidivists and may contribute to DUI persistence. Development of a DUI-specific neurocognitive assessment and greater understanding of how neurocognitive status influences DUI risk could lead to remediation strategies better adapted to the individual characteristics of recidivists.

Reduced platelet [3H]paroxetine binding in anorexia nervosa: relationship to eating symptoms and personality pathology.

Alterations in serotonin function have been implicated in both anorexia and bulimia nervosa, and previous studies suggest associations between serotonin function and variations in pathological personality traits. Women meeting DSM-IV criteria for anorexia nervosa (AN, 16 with the restricting subtype and 14 with the binge-purge subtype) and 49 healthy control women (CW) provided blood samples for analyses of platelet [(3)H]paroxetine binding. Participants also filled out questionnaires tapping eating disorder symptoms, depression, and personality pathology. Compared with CW, women with restricting and binge-purge AN had significantly lower levels of paroxetine binding (respectively: 1012 + 487 vs. 560 + 253 vs. 618 + 217 fmol/mg protein). Simple correlation analyses showed that, within AN but not within controls, paroxetine binding was inversely related to dieting preoccupations, affective instability, anxiousness, compulsivity, restricted expression and social avoidance but independent of age, body mass index, depression, and other eating symptoms. Findings suggest that reduced peripheral serotonin transporter density in AN relates to increased dieting preoccupations, affective instability and anxiousness-fearfulness.

Identification of informative strains and provisional QTL mapping of amphetamine (AMPH)-induced locomotion in recombinant congenic strains (RCS) of mice.

Amphetamine (AMPH)-induced locomotor activity is a rodent behavioral trait that reflects mesolimbic dopaminergic activity. To identify potential quantitative trait loci (QTL) associated with this behavior, we used 34 recombinant congenic strains (RCSs) of mice derived from A/J (A strains) and C57BL/6J (B strains) and measured AMPH-induced total distance traveled (AMPH-TDIST). Two strains in the A panel (A52 and A63) showed significantly elevated AMPH-TDIST compared to the parental A/J strain and behaved similarly to C57BL/6J. Simple sequence length polymorphism (SSLP) markers on chromosomes 1, 2, 3, 5, 6, 8, 9, 10 and 20 were significantly associated with AMPH-TDIST in the A strains. Within the B panel, two strains (B81 and B74) had significantly higher and two strains (B69 and B75) had significantly lower AMPH-TDIST than C57BL/6J. Markers associated with AMPH-TDIST in the B strains appeared on chromosomes 5, 17 and 20. Combining data from this approach and other genetic (mapping data in humans) and functional (cDNA expression) sources may help to identify suitable candidate genes relevant to human disorders where mesolimbic dopamine dysregulation has been postulated.

Childhood sexual abuse in relation to neurobiological challenge tests in patients with borderline personality disorder and normal controls.

This study examined whether abnormal responses to neurobiological challenge tests in borderline personality disorder (BPD) are related to a history of childhood sexual abuse (CSA). We compared patients meeting BPD criteria (n=24), with and without histories of CSA, with normal controls (n=12) on the results of challenges with meta-chlorphenylpiperazine (m-CPP), pyridostigmine and clonidine. No differences were found between abused and non-abused patients with BPD. These results do not support the hypothesis that CSA is directly related to neurobiological abnormalities in BPD.

Intrafamilial correspondences on platelet [3H-]paroxetine-binding indices in bulimic probands and their unaffected first-degree relatives.

Reduced brain serotonin (5-hydroxytryptamine: 5-HT) transporter activity has been associated with susceptibility to various forms of psychopathology, including bulimia nervosa (BN) and related syndromes characterized by appetitive or behavioural dysregulation. We applied density (Bmax) of platelet [3H-]paroxetine binding as a proxy for central 5-HT reuptake activity in two groups of women (33 with BN-spectrum disorders and 19 with no apparent eating or psychiatric disorders), most of these individuals' mothers (31 and 18, respectively), and a small sampling of their sisters (seven and eight, respectively). Hierarchical linear modeling techniques were used to account for nesting of individuals within families and diagnostic groupings. Bulimic probands, their mothers, and their sisters all displayed significantly lower density (Bmax) of platelet-paroxetine binding than did 'control' probands, mothers, or sisters-even when relatives showing apparent eating or psychiatric disturbances were excluded. In addition, in bulimic probands and mothers, significant within-family correlations were obtained on Bmax. These findings imply a heritable trait (or endophenotype), linked to 5-HT activity, and carried by BN sufferers and their first-degree relatives (even when asymptomatic). We propose that, under conducive circumstances, such a trait may increase risk of binge-eating behavior, or associated symptoms of affective or behavioral dysregulation.

Impaired platelet [3H]paroxetine binding in female patients with borderline personality disorder.

RATIONALE: There have been few studies of platelet paroxetine binding in borderline personality disorder (BPD). OBJECTIVE: Our aim was to determine whether female BPD subjects show abnormalities in platelet paroxetine binding. METHODS: Twenty-one female BPD subjects and 16 age- and gender-matched normal control subjects were assessed using the following: (1) Diagnostic Interview for Borderlines, Revised, (2) Diagnostic Assessment for Personality Pathology: Brief Questionnaire, and (3) Barratt Impulsivity Scale. Platelets were collected and assayed for platelet paroxetine binding. RESULTS: Bmax was lower in the BPD group (p < 0.0001), but differences in Kd only reached a trend level. There were no associations with trait dimensions independent of diagnosis. CONCLUSIONS: Reduced platelet paroxetine binding in female BPD patients may reflect presynaptic serotonin dysfunction.

Association of the promoter polymorphism -1438G/A of the 5-HT2A receptor gene with behavioral impulsiveness and serotonin function in women with bulimia nervosa.

Separate lines of research suggest that the functional alterations in the serotonin (5-HT) 2A receptor are associated with 5-HT tone, behavioral impulsiveness, and bulimia nervosa (BN). We explored the effect of allelic variations within the 5-HT2A receptor gene promoter polymorphism -1438G/A on trait impulsiveness and serotonin function in women with BN. Participants included women with BN having the A allele (i.e., AA homozygotes and AG heterozygotes, BNA+, N = 21); women with BN but without the A allele (i.e., GG homozygotes, BNGG, N = 12), and normal eater control women having the A allele (NEA+, N = 19) or without the A allele (NEGG; N = 9). The women were assessed for psychopathological tendencies and eating disorder symptoms, and provided blood samples for measurement of serial prolactin responses following oral administration of the post-synaptic partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP). The BNGG group had higher scores than the other groups on self-report measures of non-planning and overall impulsiveness and had blunted prolactin response following m-CPP. The bulimic groups did not differ from each other on current eating symptoms or on frequencies of other Axis I mental disorders. Findings indicate that women with BN who are GG homozygotes on the -1438G/A promoter polymorphism are characterized by increased impulsiveness and lower sensitivity to post-synaptic serotonin activation. These findings implicate the GG genotype in the co-aggregation of impulsive behaviors and alterations of post-synaptic 5-HT functioning in women with BN.

Salivary cortisol: a predictor of convictions for driving under the influence of alcohol?

AIMS: To examine the relationship between salivary cortisol and frequency of past driving under the influence of alcohol (DUI) convictions. METHODS: A total of 104 males with previous DUI convictions (from one to eight) and mean age of 44.7 years were assessed on measures characterizing repeat DUI offenders, including sociodemographic information, alcohol use behaviours, biological indices of the organic consequences of chronic abuse, negative consequences of excessive drinking, past DUI conviction history, impulse control, and antisocial behaviour tendencies. Saliva samples were taken approximately every 30 min over a 6 h period during an exhaustive multidimensional assessment protocol, and were then assayed to obtain cortisol responses. RESULTS: Blunted cortisol response, typically observed in alcoholics and in high-risk non-alcoholics, was associated with increased number of past DUI convictions. This association was particularly pronounced in multiple DUI offenders, and was stronger than, and independent of, other measures of alcohol use severity and chronicity commonly used for DUI assessment. CONCLUSIONS: Cortisol response may be useful in understanding the mediators underlying repeat DUI offending and the frequent failure of intervention efforts in curbing DUI behaviour.

Reduced density of platelet-binding sites for [3H]paroxetine in remitted bulimic women.

Findings show brain serotonin (5-hydroxytryptamine (5-HT)) activity to be altered in individuals who have had bulimia nervosa (BN), even after substantial remission of symptoms. Such findings could reflect persistent sequelae due to BN, or a vulnerability 'trait' that exists independently of active eating-disorder manifestations. We compared women with full-blown BN (BN; n=22), BN in remission (BN-R; n=11), and no eating or psychiatric disturbances (n=22) on measures of platelet [(3)H]paroxetine binding, eating symptoms and psychopathology. The BN-R group showed normal-range scores on eating and psychopathological symptoms, but reductions in density (B(max)) of binding sites for paroxetine similar to those obtained in the actively ill women. Both BN groups had substantially lower B(max) than did healthy controls. Our results corroborate other findings indicating recovered BN patients to have anomalous 5-HT functioning. While such effects could represent a lasting 'injury' to the system, reported covariations between personality traits and 5-HT indices in BN encourage us to favor the argument that some alterations of 5-HT activity (in this case, consistent with reduced transporter activity) represent a 'trait' associated with the risk of developing BN and/or associated psychopathology.

Implications of compulsive and impulsive traits for serotonin status in women with bulimia nervosa.

Studies of bulimia nervosa (BN) often report decreased brain serotonin (5-hydroxytryptamine: 5-HT) activity. Across populations, impulsivity has been linked to reduced 5-HT activity, but compulsivity has been associated (at least inconsistently) with an increase. We therefore became interested in the association between behavioral-trait variations and 5-HT status in BN. In 56 bulimic and 29 non-bulimic women, we measured eating symptoms, personality traits, platelet paroxetine binding, and neuroendocrine responses following oral meta-chlorophenylpiperazine (m-CPP). Relative to normal eaters, bulimic women showed reduced density (Bmax) of platelet paroxetine-binding sites, blunted prolactin (PRL) responses following m-CPP, and (as a trend) lower basal PRL levels. However, after effects of binge-purge frequencies, body mass, and other extraneous factors were controlled, PRL levels at baseline and other moments in the serial sampling varied systematically with presence of impulsive and compulsive traits. PRL was generally low in BN, but 'high-compulsive'/'low-impulsive' traits were associated with higher (normal-range) PRL values. Comparable trait-related variations were not observed on paroxetine-binding indices. Our findings suggest that 5-HT status in BN may correspond to impulsive or compulsive traits, and they encourage multidimensional modeling of the pathophysiological role of 5-HT in BN.

Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids.

In a previous longitudinal study of basal cortisol levels and cognitive function in humans, we showed that elderly humans with 4- to 7-yr cumulative exposure to high levels of cortisol present memory impairments, compared with elderly humans with moderate cortisol levels over years. Here, we measured whether memory performance in two groups of elderly humans separated on the basis of their cortisol history over a 5-yr period could be modulated by a hormone-replacement protocol in which we inhibited cortisol secretion by the administration of metyrapone and then restored baseline cortisol levels by infusion of hydrocortisone. We showed that in elderly subjects with a 5-yr history of moderate cortisol levels (n = 8), metyrapone treatment significantly impaired memory performance, a deficit that was reversed following hydrocortisone replacement. In the elderly subjects with a 5-yr history of high cortisol levels and current memory deficits (n = 9), metyrapone treatment did not have any significant effect on memory performance, but hydrocortisone treatment significantly decreased delayed memory. These results suggest that memory function in elderly humans can be intensely modulated by pharmacological manipulation of glucocorticoids, although the direction of these effects depends on the cortisol history of each individual.

The modulatory effects of corticosteroids on cognition: studies in young human populations.

In the present article, we report on two studies performed in young human populations which tested the cognitive impact of glucocorticoids (GC) in situations of decreased or increased ratio of mineralocorticoid (MR) and glucocorticoid (GR) receptor occupation. In the first study, we used a hormone replacement protocol in which we pharmacologically decreased cortisol levels by administration of metyrapone and then restored baseline cortisol levels by a subsequent hydrocortisone replacement treatment. Memory function was tested after each pharmacological manipulation. We observed that metyrapone treatment significantly impaired delayed recall, while hydrocortisone replacement restored performance at placebo level. In the second study, we took advantage of the circadian variation of circulating levels in cortisol and tested the impact of a bolus injection of 35 mg of hydrocortisone in the late afternoon, at a time of very low cortisol concentrations. In a previous study with young normal controls, we injected a similar dose of hydrocortisone in the morning, at the time of the circadian peak, and reported detrimental effects of GC on cognitive function. Here, when we injected a similar dose of hydrocortisone in the afternoon, at the time of the circadian trough, we observed positive effects of GC on memory function. The results of these two studies provide evidence that GC are necessary for learning and memory in human populations.