Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy.

A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks.

Participants with higher scores on the need for medical reassurance factor of the Panic–Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission.

This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Panic disorder (PD) is a heterogeneous syndrome that can present with a variety of symptom profiles that potentially reflect distinct etiologic pathways. The present study represents the most comprehensive examination of phenotypic variance in PD with and without agoraphobia for the purpose of identifying clinically relevant and etiologically meaningful subtypes.

Latent class (LC) and factor mixture analysis were used to examine panic symptom data ascertained from three national epidemiologic surveys [Epidemiological Catchment Area (ECA), National Comorbidity Study (NCS), National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), Wave 1], a twin study [Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD)] and a clinical trial (Cross-National Collaborative Panic Study [CNCPS]).

Factor mixture models (versus LC) generally provided better fit to panic symptom data and suggested two panic classes for the ECA, VATSPSUD and CNCPS, with one class typified by prominent respiratory symptoms. The NCS yielded two classes, but suggested both qualitative and quantitative differences. The more contemporary NESARC sample supported a two and three class model, with the three class model suggesting two variants of respiratory panic. The NESARC's three class model continued to provide the best fit when the model was restricted to a more severe form of PD/panic disorder with agoraphobia.

Results from epidemiologic and clinical samples suggest two panic subtypes, with one subtype characterized by a respiratory component and a second class typified by general somatic symptoms. Results are discussed in light of their relevance to the etiopathogenesis of PD.

Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition.

A total of 3021 community subjects (97.7% lifetime AU) aged 14–24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI.

Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition.

Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD.

Anorexia nervosa (AN), at the stage of starvation and emaciation, is characterized by abnormalities in cognitive function, including memory performance. It is unclear whether memory impairment persists or is reversible following weight restoration, and whether memory function differs between AN subtypes. The aim of the present study was to investigate general memory performance in currently ill and fully weight-restored patients of different AN subtypes.

Memory performance was assessed using the Wechsler Memory Scale-Revised (WMS-R) in a total of 99 participants, including 34 restricting-type AN patients (AN-RESTR), 19 binge-eating/purging-type AN patients (AN-PURGE), 16 weight-restored AN patients (AN-W-R) and 30 healthy controls (CONTROL). Cognitive evaluation included a battery of standardized neuropsychological tasks for validating the findings on memory function.

Deficits were found with respect to immediate and delayed story recall in currently ill AN patients irrespective of AN subtype. These deficits persisted in weight-restored AN patients. Currently ill and weight-restored AN patients did not differ significantly from healthy controls with respect to working memory or other measures of neuropsychological functioning.

The findings suggest that impaired memory performance is either a stable trait characteristic or a scar effect of chronic starvation that may play a role in the development and/or persistence of the disorder.

Impairments in working memory are present in many psychiatric illnesses such as attention-deficit hyperactivity disorder (ADHD) and schizophrenia. The dopamine transporter and catechol-O-methyltransferase (COMT) are proteins involved in dopamine clearance and the dopamine system is implicated in the modulation of working memory (WM) processes and neurochemical models of psychiatric diseases. The effects of functional polymorphisms of the dopamine transporter gene (DAT1) and the COMT gene were investigated using a visuospatial and numerical n-back working memory paradigm. Our n-back task was designed to reflect WM alone, and made no demands on higher executive functioning.

A total of 291 healthy volunteers (aged 18–45 years) were genotyped and matched for age, sex, and Barratt Impulsivity Scale (BIS) and National Adult Reading Test (NART) scores. To assess individual gene effects on WM, factorial mixed model analysis of variances (ANOVAs) were conducted with the between-subjects factor as genotype and difficulty level (0-, 1-, 2- and 3-back) entered as the within-subjects factor.

The analysis revealed that the DAT1 or COMT genotype alone or in combination did not predict performance on the n-back task in our sample of healthy volunteers.

Behavioral effects of DAT1 and COMT polymorphisms on WM in healthy volunteers may be non-existent, or too subtle to identify without exceedingly large sample sizes. It is proposed that neuroimaging may provide more powerful means of elucidating the modulatory influences of these polymorphisms.

Executive functions have been proposed as endophenotypes for attention deficit hyperactivity disorder (ADHD); however, data regarding visual memory are lacking. We therefore assessed visual memory in adolescents with ADHD and their unaffected siblings compared with controls.

The participants included 279 adolescents with ADHD, 108 unaffected siblings, and 173 unaffected school controls. They were assessed by using the visual memory tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Delayed Matching to Sample (DMS), Spatial Recognition Memory (SRM), Paired Associates Learning (PAL), and Pattern Recognition Memory (PRM).

Compared with the controls, probands with ADHD had a significantly lower number of correct responses, a higher probability of an error following a correct response and following an error response in the DMS, and a lower percentage of correct responses in the SRM. Their unaffected siblings occupied an intermediate position between ADHD probands and controls in the probability of an error following a correct response and following an error response in the DMS, and in the percentage of correct responses in the SRM. In general, lower IQ and current use of and duration of treatment with methylphenidate were associated with more severe visual memory deficits.

The present results suggest that ADHD is associated with poorer visual memory function. Visual memory assessed by the DMS and SRM tasks in the CANTAB may be a useful endophenotype for ADHD.

Anorexia nervosa (AN) is a serious psychiatric illness associated with significant morbidity and mortality. There is little empirical support for specific treatments and new approaches are sorely needed. This two-site study aimed to determine whether olanzapine is superior to placebo in increasing body mass index (BMI) and improving psychological symptoms in out-patients with AN.

A total of 23 individuals with AN were randomly assigned in double-blind fashion to receive olanzapine or placebo for 8 weeks together with medication management sessions that emphasized compliance. Weight, other physical assessments and measures of psychopathology were collected.

End-of-treatment BMI, with initial BMI as a covariate, was significantly greater in the group receiving olanzapine [F(1, 20)=6.64, p=0.018]. Psychological symptoms improved in both groups, but there were no statistically significant group differences. Of the 23 participants, 17 (74%) completed the 8-week trial. Participants tolerated the medication well with sedation being the only frequent side effect and no adverse metabolic effects were noted.

This small study suggests that olanzapine is generally well tolerated by, and may provide more benefit than placebo for out-patients with AN. Further study is indicated to determine whether olanzapine may affect psychological symptoms in addition to BMI.

Schizophrenia patients demonstrate impairment on visual backward masking, a measure of early visual processing. Most visual masking paradigms involve two distinct processes, an early fast-acting component associated with object formation and a later component that acts through object substitution. So far, masking paradigms used in schizophrenia research have been unable to separate these two processes.

We administered three visual processing paradigms (location masking with forward and backward masking, four-dot backward masking and a cuing task) to 136 patients with schizophrenia or schizoaffective disorder and 79 healthy controls. A psychophysical procedure was used to match subjects on identification of an unmasked target prior to location masking. Location masking interrupts object formation, four-dot masking task works through masking by object substitution and the cuing task measures iconic decay.

Patients showed impairment on location masking after being matched for input threshold, similar to previous reports. After correcting for age, patients showed lower performance on four-dot masking than controls, but the groups did not differ on the cuing task.

Patients with schizophrenia showed lower performance when masking was specific to object substitution. The difference in object substitution masking was not due to a difference in rate of iconic decay, which was comparable in the two groups. These results suggest that, despite normal iconic decay rates, individuals with schizophrenia show impairment in a paradigm of masking by object substitution that did not also involve disruption of object formation.

The aim of this study was to explore the extent of lack of insight and its components in eating disorders (EDs) and to investigate the relationship between insight and clinical and cognitive characteristics in this group.

Seventy-five participants were enrolled in the study: 25 with anorexia nervosa (AN), 15 with bulimia nervosa (BN) and 35 healthy controls (HC). Insight was assessed with a modified version of the Schedule for the Assessment of Insight for EDs (SAI-ED) and multi-dimensional scaling (MDS) analysis was used to clarify the internal structure of the scale. Neuropsychological tests included the Trail Making Test (TMT), the Brixton Test and a Verbal Fluency Task.

Only a subgroup of AN patients (24%) had severe impairment of insight. Patients with the restricting type of AN (AN-R) had poorer overall insight than patients with the binge-purge type of the disorder (AN-B/P). More of the ED patients displayed a deliberate denial of illness rather than a lack of awareness of the illness. A regression model revealed that only performance in part B of the TMT (TMT-B) was a moderate predictor of insight level. No association was found between insight and other cognitive or clinical variables.

Impaired insight is a significant feature of some ED patients. Insight in EDs seems to be partially dependent on intact mental flexibility.

Pre-menstrual dysphoric disorder (PMDD) is commonly studied in white women; consequently, it is unclear whether the prevalence of PMDD varies by race. Although a substantial proportion of black women report symptoms of PMDD, the Biocultural Model of Women's Health and research on other psychiatric disorders suggest that black women may be less likely than white women to experience PMDD in their lifetimes.

Multivariate multinomial logistic regression modeling was used with a sample of 2590 English-speaking, pre-menopausal American women (aged 18–40 years) who participated in the Collaborative Psychiatric Epidemiology Surveys in 2001–2003. The sample consisted of 1672 black women and 918 white women. The measure of PMDD yields a provisional diagnosis of PMDD consistent with DSM-IV criteria.

Black women were significantly less likely than white women to experience PMDD [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.25–0.79] and pre-menstrual symptoms (OR 0.64, 95% CI 0.47–0.88) in their lifetimes, independently of marital status, employment status, educational attainment, smoking status, body mass index, history of oral contraceptive use, current age, income, history of past-month mood disorder, and a measure of social desirability. The prevalence of PMDD was 2.9% among black women and 4.4% among white women.

This study showed for the first time that black women were less likely than white women to experience PMDD and pre-menstrual symptoms, independently of relevant biological, social-contextual and psychological risk factors. This suggests that PMDD may be an exception to the usual direction of racial disparities in health. Further research is needed to determine the mechanisms that explain this health advantage.

Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically informative design to assess whether these traits share a common genetic and/or environmental liability.

We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU.

The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD–RU and MD–ND relationships are partially attributable to genetic and unique environmental correlations.

The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate.

There is a lack of consistent evidence regarding associations of neurological soft signs (NSS) with illness-related variables in schizophrenia. This study examined NSS in first-episode psychotic patients with respect to their factor structure and associations with risk factors, pre-morbid characteristics, psychopathology and spontaneous extrapyramidal syndromes.

First-episode, drug-naive patients with schizophrenia-spectrum disorders (n=177) were assessed for NSS using the Neurological Evaluation Scale, and its 26 constituting items were factor analysed. The identified neurological dimensions were then entered into hierarchical regression models as outcome dependent variables of a set of predictors including risk factors (familial loading for schizophrenia, obstetric complications), pre-morbid characteristics (neurodevelopmental delay, symptoms of attention deficit–hyperactivity disorder, pre-morbid functioning), psychopathological domains (reality distortion, disorganization, negative symptoms, mania, depression, catatonia) and spontaneous extrapyramidal syndromes (parkinsonism, dyskinesia, akathisia).

Five neurological domains were identified: sequencing, release signs, sensory integration, abnormal movements and coordination. Multivariate analyses showed independent associations (p<0.01) of sequencing with familial liability to schizophrenia, deterioration of pre-morbid adjustment and parkinsonism; release signs with obstetric complications, catatonic symptoms and parkinsonism; sensory integration with familial liability to schizophrenia; abnormal movements with familial liability to schizophrenia, obstetric complications, parkinsonism and dyskinesia; and coordination with neurodevelopmental delay. The empirically derived factors explained additional variance over and above that explained by subscale scores across the examined variables.

Familial liability to schizophrenia, obstetric complications, neurodevelopmental delay, deterioration in pre-morbid functioning and observable motor disorders appear to contribute independently to domains of neurological dysfunction. The findings support a neurodevelopmental model of NSS in schizophrenia.

The aim was to examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the US general population.

Respondents in the National Comorbidity Survey Replication with common 12-month DSM-IV mood, anxiety, substance, impulse control and childhood disorders were asked about perceived need for treatment, structural barriers and attitudinal/evaluative barriers to initiation and continuation of treatment.

Low perceived need was reported by 44.8% of respondents with a disorder who did not seek treatment. Desire to handle the problem on one's own was the most common reason among respondents with perceived need both for not seeking treatment (72.6%) and for dropping out of treatment (42.2%). Attitudinal/evaluative factors were much more important than structural barriers both to initiating (97.4% v. 22.2%) and to continuing (81.9% v. 31.8%) of treatment. Reasons for not seeking treatment varied with illness severity. Low perceived need was a more common reason for not seeking treatment among individuals with mild (57.0%) than moderate (39.3%) or severe (25.9%) disorders, whereas structural and attitudinal/evaluative barriers were more common among respondents with more severe conditions.

Low perceived need and attitudinal/evaluative barriers are the major barriers to treatment seeking and staying in treatment among individuals with common mental disorders. Efforts to increase treatment seeking and reduce treatment drop-out need to take these barriers into consideration as well as to recognize that barriers differ as a function of sociodemographic and clinical characteristics.

Autism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of ‘peaks’ and ‘troughs’ at the subtest level. However, there are few data from epidemiological studies.

Comprehensive clinical assessments were conducted with 156 children aged 10–14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population.

Of the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbal versus performance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no ‘peak’ in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ.

In this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.

Early diagnosis of dementia requires knowledge about associated predictors. The aim of this study was to determine the impact of mild cognitive impairment (MCI) and impairment in instrumental activities of daily living (IADL) on the time to an incident dementia diagnosis.

Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+), a population-based study of individuals aged ⩾75 years. Kaplan-Meier survival analysis was used to determine time to incident dementia. Cox proportional hazards models were applied to determine the impact of MCI and IADL impairment on the time to incident dementia.

In total, 180 (22.0%) of 819 initially dementia-free subjects developed dementia by the end of the study. Mean time to incident dementia was 6.7 years [95% confidence interval (CI) 6.5–6.9]. MCI combined with IADL impairment was associated with a higher conversion rate to dementia, a shorter time to clinically manifest diagnosis and a lower chance of reversibility to cognitive normal. The highest risk for a shorter time to incident dementia was found for amnestic MCI combined with IADL impairment. The mean time to incident dementia was 3.7 years (95% CI 2.9–4.4) and thus half as long as in subjects without MCI and IADL impairment.

Subjects with MCI and IADL impairment constitute a high-risk population for future dementia. The consideration of both – MCI and IADL impairment – might help to improve the prediction of dementia.

Autistic-like traits (ALTs), that is restrictions in intuitive social interaction, communication and flexibility of interests and behaviors, were studied in two population-based Swedish twin studies, one in children and one in adults: (1) to examine whether the variability in ALTs is a meaningful risk factor for concomitant attention deficit hyperactivity disorder (ADHD), anxiety, conduct problems, depression and substance abuse, and (2) to assess whether common genetic and environmental susceptibilities can help to explain co-existence of ALTs and traits associated with such concomitant problems.

Two nationwide twin cohorts from Sweden (consisting of 11 222 children and 18 349 adults) were assessed by DSM-based symptom algorithms for autism. The twins were divided into six groups based on their degree of ALTs and the risk for concomitant mental health problems was calculated for each group. Genetic and environmental susceptibilities common to ALTs and the other problem types were examined using bivariate twin modeling.

In both cohorts, even the lowest degree of ALTs increased the risk for all other types of mental health problems, and these risk estimates increased monotonically with the number of ALTs. For all conditions, common genetic and environmental factors could be discerned. Overall, the phenotypic correlation between ALTs and the traits examined were less pronounced in adulthood than in childhood and less affected by genetic compared with environmental factors.

Even low-grade ALTs are relevant to clinical psychiatry as they increase the risk for several heterotypical mental health problems. The association is influenced partly by common genetic and environmental susceptibilities. Attention to co-existing ALTs is warranted in research on a wide range of mental disorders.

Studies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN.

Attention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17β-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory – Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery–Asberg Depression Rating Scale (MADRS) were administered.

No impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and ‘Self-directedness’ were associated with better performance on conditional learning whereas 17β-estradiol had a negative influence on this domain; ‘Reward dependence’ was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively.

No cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings.

The few genetically informative studies to examine post-traumatic stress disorder (PTSD) and alcohol dependence (AD), all of which are based on a male veteran sample, suggest that the co-morbidity between PTSD and AD may be attributable in part to overlapping genetic influences, but this issue has yet to be addressed in females.

Data were derived from an all-female twin sample (n=3768) ranging in age from 18 to 29 years. A trivariate genetic model that included trauma exposure as a separate phenotype was fitted to estimate genetic and environmental contributions to PTSD and the degree to which they overlap with those that contribute to AD, after accounting for potential confounding effects of heritable influences on trauma exposure.

Additive genetic influences (A) accounted for 72% of the variance in PTSD; individual-specific environmental (E) factors accounted for the remainder. An AE model also provided the best fit for AD, for which heritability was estimated to be 71%. The genetic correlation between PTSD and AD was 0.54.

The heritability estimate for PTSD in our sample is higher than estimates reported in earlier studies based almost exclusively on an all-male sample in which combat exposure was the precipitating traumatic event. However, our findings are consistent with the absence of evidence for shared environmental influences on PTSD and, most importantly, the substantial overlap in genetic influences on PTSD and AD reported in these investigations. Additional research addressing potential distinctions by gender in the relative contributions of genetic and environmental influences on PTSD is merited.

Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response.

Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine.

Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified.

This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.

An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain.

Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain.

In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients.

Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.