Comprehensive neurocognitive assessment of patients with anorexia nervosa

AIM: To utilise a comprehensive cognitive battery to gain a better understanding of cognitive performance in anorexia nervosa (AN).METHODS: Twenty-six individuals with AN and 27 healthy control participants matched for age, gender and premorbid intelligence, participated in the study. A standard cognitive battery, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery, was used to investigate performance on seven cognitive domains with the use of 10 different tasks: speed of processing [Brief Assessment Of Cognition In Schizophrenia: Symbol Coding, Category Fluency: Animal Naming (Fluency) and Trail Making Test: Part A], attention/vigilance [Continuous Performance Test - Identical Pairs (CPT-IP)], working memory [Wechsler Memory Scale (WMS^®-III): Spatial Span, and Letter-Number Span (LNS)], verbal learning [Hopkins Verbal Learning Test - Revised], visual learning [Brief Visuospatial Memory Test - Revised], reasoning and problem solving [Neuropsychological Assessment Battery: Mazes], and social cognition [Mayer-Salovey-Caruso Emotional Intelligence Test: Managing Emotions]. Statistical analyses involved the use of multivariate and univariate analyses of variance.RESULTS: Analyses conducted on the cognitive domain scores revealed no overall significant difference between groups nor any interaction between group and domain score [F(1,45) = 0.73, P = 0.649]. Analyses conducted on each of the specific tasks within the cognitive domains revealed significantly slower reaction times for false alarm responses on the CPT-IP task in AN [F(1,51) = 12.80, P < 0.01, Cohen’s d = 0.982] and a trend towards poorer performance in AN on the backward component of the WMS^®-III Spatial Span task [F(1,51) = 5.88, P = 0.02, Cohen’s d = -0.665]. The finding of slower reaction times of false alarm responses is, however, limited due to the small number of false alarm responses for either group.CONCLUSION: The findings are discussed in terms of poorer capacity to manipulate and process visuospatial material in AN.     

Suicide attempts and mortality in eating disorders: a follow-up study of eating disorder patients

Objective

The aim of this study is to explore the prevalence of hospital-treated suicide attempts in a large clinical population of eating disorder patients.

Method

Follow-up study of adults (N= 2462, 95% women, age 18–62 years) admitted to the Eating Disorder Clinic of Helsinki University Central Hospital in the period 1995–2010. For each patient, four controls were selected and matched for age, sex and place of residence. The end point events were modeled using Cox’s proportional hazard model, taking matching into account.

Results

We identified 156 patients with eating disorder (6.3%) and 139 controls (1.4%) who had required hospital treatment for attempted suicide. Of them, 66 (42.3%) and 37 (26.6%) had more than one attempt. The rate ratio (RR) for suicide attempt in patients with eating disorder was 4.70 [95% confidence interval (CI) 1.41–15.74]. In anorexia nervosa, RR was 8.01 (95% CI 5.40–11.87), and in bulimia nervosa, it was 5.08 (95% CI 3.46–7.42). In eating disorder patients with a history of suicide attempt, the risk of death from any cause was 12.8%, suicide being the main cause in 45% of the deaths.

Conclusion

Suicide attempts and repeated attempts are common among patients with eating disorders. Suicidal ideation should be routinely assessed from patients with eating disorders.     

Recent medical service utilization and health conditions associated with a history of suicide attempts

Objectives

Suicide is a leading cause of death; unfortunately most individuals at risk for suicide are not identified, assessed or treated by the mental health system. Investigating medical healthcare utilization among individuals with a history of suicide attempt may identify alternative settings for case finding and brief intervention.

Methods

The study sample (n= 1422, 58% female, 72% African-American) is from a prospective cohort of adults (27–31 years) who participated in a randomized trial of school-based interventions. Logistic regression evaluated the relationship between lifetime history of suicide attempt with past year medical service utilization and selected self- reported health conditions, controlling for lifetime Major Depressive Disorder (MDD), demographic factors, health insurance status and employment.

Results

A suicide attempt history was associated with past year emergency department medical visits [aOR 1.51, 95% CI 1.04–2.18, P= .03], but not primary care visits or inpatient hospitalization, when controlling for MDD and other covariates. Severe headaches and chronic gastrointestinal conditions were also associated with lifetime suicide attempt [aOR 1.50, 95% CI 1.03–2.17 and aOR 1.67, 95% CI 1.06–2.63, respectively].

Conclusions

Suicide prevention, including universal screening and brief intervention, is indicated in emergency department settings. Restricting screening to subgroups, such as those individuals presenting with depression, may miss at-risk individuals with somatic concerns.     

Impact of broadening definitions of anorexia nervosa on sample characteristics

Practical limitations and sample size considerations often lead to broadening of diagnostic criteria for anorexia nervosa (AN) in research. The current study sought to elucidate the effects of this practice on resultant sample characteristics in terms of eating disorder behaviors, psychiatric comorbidities, temperament and personality characteristics, and heritability point estimates. Three definitions of AN were created: meeting all Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for AN (AN-DSM-IV), meeting all DSM-IV criteria except criterion D, amenorrhea, (AN-noD), and broadening DSM-IV AN criteria by allowing a higher body mass index value, eliminating criterion D, and allowing less stringent body weight concerns (AN-Broad). Using data from the Swedish Twin Registry, 473 women fit one of the three definitions of AN. Women with AN-DSM-IV reported significantly more eating disorder behaviors than women with AN-Broad. Women with AN-noD reported more comorbid psychiatric disorders than women with AN-DSM-IV and AN-Broad. Temperament and personality characteristics did not differ across the three groups. Heritability point estimates decreased as AN definition broadened. Broadening the diagnostic criteria for AN results in an increased number of individuals available for participation in research studies. However, broader criteria for AN yield a more heterogeneous sample with regard to eating disorder symptoms and psychiatric comorbidity than a sample defined by narrower criteria.     

Different characteristics associated with suicide attempts among bipolar I versus bipolar II disorder patients

BackgroundSuicide attempts are common in patients with bipolar disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with bipolar I disorder (BDI) versus bipolar II disorder (BDII)).MethodsOutpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype.ResultsAmong 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes.LimitationsAmerican tertiary bipolar disorder clinic referral sample, cross-sectional design.ConclusionsFurther studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII.     

The intellectual functioning of adolescents with anorexia nervosa and bulimia nervosa

The aim of this study was to investigate the intellectual functioning of a large group of eating disordered adolescents in order to test two hypotheses, viz, that the intellectual functioning of eating disordered adolescents conforms to the normal distribution, and that eating disordered adolescents do not perform better in verbal abilities than in nonverbal abilities. Standard intelligence tests were applied to 190 consecutive out- and inpatients with eating disorder diagnoses. The results were compared with those of a group of patients with other disorders, similar in age, sex, SES, and year of admission. The IQ of the eating disordered patients was significantly higher than that of patients in the comparison group. Patients in the comparison group and bulimic patients, but not anorexic patients, showed better nonverbal than verbal intellectual performance.     

Lower body weight is associated with less negative emotions in sad autobiographical memories of patients with anorexia nervosa

Food restriction and weight-loss have been proposed to represent pathogenic mechanisms of emotion regulation in anorexia nervosa (AN). However, there is a lack of studies empirically examining this hypothesis. Therefore, the present study compared 25 women with AN and 25 healthy control women (HC) regarding spontaneous emotional processing of autobiographic memories. Participants' idiographic memories of sad autobiographic events were analyzed using computerized, quantitative text analysis as an unobtrusive approach of nonreactive assessment. Compared to HC, AN patients retrieved more negative but a comparable number of positive emotions. Moreover, the lesser the body weight in AN patients, the lesser negative emotions they retrieved, irrespective of current levels of depressive symptoms and duration of illness. No such association was found in HC. These preliminary findings are in line with models of AN proposing that food restriction and weight-loss may be negatively reinforced by the alleviation of aversive emotional responses.     

Molecular mechanisms underlying anorexia nervosa: Focus on human gene association studies and systems controlling food intake

Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-β (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-α)). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.     

Efficacy of psychotherapy on diurnal cortisol patterns and suicidal ideation in adjustment disorder with depressed mood

Aims

The aims were to examine the effects of psychotherapy on depressive and anxiety symptoms, the occurrence of suicidal ideations and diurnal cortisol patterns in patients with adjustment disorder (AD) with depressed mood.

Methods

Participants recruited from an outpatient department of psychiatry at a general hospital were randomly assigned to one of two groups: 34 in psychotherapy group and 37 in control group. The control group consisted of one-session psychoeducation. Psychotherapy included the eight-weekly body–mind–spirit (BMS) group psychotherapy. Measures included Beck Depression Inventory-II and State Trait Anxiety Inventory. Salivary cortisol samples were collected from the patients at their homes on awakening; 30 and 45min after awakening; and at 1200, 1700 and 2100 h. Measurements were taken at baseline and at months 2 (end of intervention), 5, 8 and 14.

Results

There was no differential change over time between the BMS and control groups in self-reported depression or anxiety symptoms. However, suicidal ideation appeared to be reduced in the psychotherapy group. Changes in diurnal cortisol patterns were also significantly different in group × time interactions, in favor of BMS group.

Conclusions

Psychotherapy likely provides improvements in psychobiological stress responses and decreases the occurrence of suicidal ideation in patients with AD.     

Brain volume reduction predicts weight development in adolescent patients with anorexia nervosa

BackgroundAcute anorexia nervosa (AN) is associated with marked brain volume loss potentially leading to neuropsychological deficits. However, the mechanisms leading to this brain volume loss and its influencing factors are poorly understood and the clinical relevance of these brain alterations for the outcome of these AN-patients is yet unknown.MethodsBrain volumes of 56 female adolescent AN inpatients and 50 healthy controls (HCs) were measured using MRI scans. Multiple linear regression analyses were used to determine the impact of body weight at admission, prior weight loss, age of onset and illness duration on volume loss at admission and to analyse the association of brain volume reduction with body weight at a 1-year follow-up (N = 25).ResultsCortical and subcortical grey matter (GM) and cortical white matter (WM) but not cerebellar GM or WM were associated with low weight at admission. Amount of weight loss, age of onset and illness duration did not independently correlate with any volume changes. Prediction of age-adjusted standardized body mass index (BMI-SDS) at 1-year follow-up could be significantly improved from 34% of variance explained by age and BMI-SDS at admission to 47.5–53% after adding cortical WM, cerebellar GM or WM at time of admission.ConclusionWhereas cortical GM changes appear to be an unspecific reflection of current body weight (“state marker”), cortical WM and cerebellar volume losses seem to indicate a longer-term risk (trait or “scar” of the illness), which appear to be important for the prediction of weight rehabilitation and long-term outcome.     

On the role of impulsivity and decision-making in suicidal behavior

Suicide risk constitutes a complex set of interacting demographic, clinical, psychobiological and environmental variables. Impulsivity is a long-known risk factor for suicide attempts. However, research based on clearer conceptual refinement in this area is imperative. One emerging field of study is that of decision-making. Impulsivity involves a failure of higher-order control, including decision-making. Using standardized operational definitions that take into consideration relevant aspects of impulsivity, including state- and trait-components and a deeper understanding of the process of decision-making in the suicidal mind, we may come a step closer to understanding suicidality and winning the fight in this scourge of human suffering.     

Evidence of complex involvement of serotonergic genes with restrictive and binge purge subtypes of anorexia nervosa

Abstract

Objectives. There is mixed evidence of association of serotoninergic genes with anorexia nervosa (AN), but substantial evidence for the involvement of serotonergic mechanisms in appetite control. This study was designed to investigate possible associations between the two subtypes of AN (Restricting-RAN, and Binge-purging–BPAN) and polymorphisms within five genes encoding for proteins involved in the serotoninergic system. Methods. In order to carry out this investigation we have conducted a case–control association study on 226 females meeting the criteria for AN, and 678 matched healthy females. Results. Our data show a significant association between polymorphisms with the gene encoding HTR2A with both AN subtypes, an association between polymorphisms within the genes encoding HTR1D and HTR1B with RAN, and an association between polymorphisms within the gene encoding HTR2C with BPAN. No associations were found for any polymorphisms of the serotonin transporter gene. This outcome indicates a substantial and complex inter-relationship between serotoninergic genes and AN. Conclusions. Given these data we hypothesis that the expression or control of expression of several genes of the serotoninergic system, and interactions between these genes, could exert considerable influence over the specific symptomatology of the subtypes of AN.     

抑郁症患者自杀风险评估的事件相关电位研究进展

多项研究显示,事件相关电位(ERP)可通过无创性检测抑郁症患者认知功能,进而评估其自杀风险。本文综述了相关的ERP成分在评估抑郁症患者自杀风险中的研究进展,以期为临床评估自杀风险提供参考。     

Autobiographical memory deficit in anorexia nervosa: emotion regulation and effect of duration of illness

Emotional deficits in anorexia nervosa can be expressed in autobiographical memory recall. The aim of this study is to test whether deficits in autobiographical memory exist in anorexic patients and concern specifically negative or positive emotional valence. Moreover, it is unclear whether these deficits are dependent upon comorbid aspects (depression, alexithymia, and anxiety) or upon illness duration. Anorexic patients (n=25) were compared to healthy volunteers based on their clinical assessment, explicit memory test score, and autobiographical memory test score. The study makes use of the autobiographical test of Williams and Scott, which involves specific emotional cues to elicit memory. Anorexic patients recalled more general memories than controls in autobiographical memory test, but had no deficit in explicit memory test. This pattern, observed both for negative and positive cues, was neither related to depression or alexithymia, nor to anxiety severity, but increased significantly with illness duration. These results show that anorexic patients are characterized by relative difficulty in the integration of both negative and positive emotional experiences, and that this impairment is reinforced by illness duration.     

In vivo evidence of global and focal brain alterations in anorexia nervosa

Brain alterations are known to be associated with anorexia nervosa (AN) and tend to be distributed across brain structures, with only a few reports describing focal damage. Magnetic resonance images of 21 anorexic patients with different disease duration and 27 control subjects were acquired and compared using voxel-based morphometry (VBM). Patients had a significant reduction of total white matter (WM) volume and focal gray matter (GM) atrophy in cerebellum, hypothalamus, caudate nucleus and frontal, parietal and temporal areas. The cerebellum was more affected in patients with longer disease duration, whereas the hypothalamic alterations were more pronounced in patients with shorter food restriction. A correlation with body mass index (BMI) and GM was found in the hypothalamus. Our data demonstrate a diffuse reduction of WM together with focal areas of GM atrophy in AN. The finding of a hypothalamic focal atrophy points to hormonal dysfunction and opens the possibility for a central dysregulation of homeostasis. The involvement of temporoparietal areas could account for body image distortion. Finally, the cerebellar GM atrophy confirms previous findings and seems to be a late consequence of AN that could play a role in the chronic phase of the disease.     

Dialectical behaviour therapy and an added cognitive behavioural treatment module for eating disorders in women with borderline personality disorder and anorexia nervosa or bulimia nervosa who failed to respond to previous treatments. An open trial with a 15-month follow-up

There is evidence from case studies suggesting that adapted dialectical behavior therapy (DBT) for borderline personality disorder (BPD) and eating disorders (ED) might improve disorder related complaints. Twenty-four women with BPD (9 with comorbid anorexia nervosa [AN] and 15 with bulimia nervosa [BN]), who already had failed to respond to previous eating-disorder related inpatient treatments were consecutively admitted to an adapted inpatient DBT program. Assessment points were at pre-treatment, post-treatment, and 15-month follow-up. At follow-up, the remission rate was 54% for BN, and 33% for AN. Yet 44% of women with AN crossed over to BN and one woman additionally met the criteria of AN. For women with AN, the mean weight was not significantly increased at post-treatment, but had improved at follow-up. For women with BN, the frequency of binge-eating episodes was reduced at post-treatment as well as at follow-up. Self-rated eating-related complaints and general psychopathology, as well as ratings on global psychosocial functioning, were significantly improved at post-treatment and at follow-up. Although these findings support the assumption that the adapted DBT inpatient program is a potentially efficacious treatment for those who failed to respond to previous eating-disorder related inpatient treatments, remission rates and maintained eating-related psychopathology also suggest that this treatment needs further improvement.     

Recovery and chronicity in anorexia nervosa: brain activity associated with differential outcomes.

BACKGROUND: The course of anorexia nervosa varies from rapid recovery to a chronic debilitating illness. This study aimed to identify functional neural correlates associated with differential outcomes. METHODS: Brain reactions to food and emotional visual stimuli were measured with functional magnetic resonance imaging in nine women who had long-term recovery from restricting anorexia nervosa. These were compared with age- and education-matched groups of eight women chronically ill with restricting anorexia nervosa and nine healthy control women. RESULTS: In response to food stimuli, increased medial prefrontal and anterior cingulate activation, as well as a lack of activity in the inferior parietal lobule, differentiated the recovered group from the healthy control subjects. Increased activation of the right lateral prefrontal, apical prefrontal, and dorsal anterior cingulate cortices differentiated these recovered subjects from chronically ill patients. Group differences were specific to food stimuli, whereas processing of emotional stimuli did not differ between groups. CONCLUSIONS: Separate neural correlates underlie trait and state characteristics of anorexia nervosa. The medial prefrontal response to disease-specific stimuli may be related to trait vulnerability. Lateral and apical prefrontal involvement is associated with a good outcome.     

抑郁症与焦虑障碍共病临床特征研究

目的 调查抑郁症和焦虑症障碍的共病率,以及对临床严重程度的影响.方法 采用前瞻性、多中心、队列研究.入组对象符合美国精神障碍诊断与统计手册(第4版)抑郁症的诊断标准, 采用17项汉密尔顿抑郁量表(HAMD)和焦虑量表(HAMA),社会功能缺陷筛选量表(SSDS)和临床大体量表(CGI)评估.观察流行病学资料,焦虑和抑郁症状群、自杀状况.用情感性障碍和精神分裂症检查提纲中有关焦虑障碍的诊断清单评定患者合并的焦虑障碍.结果 共入组508例患者,首次抑郁发作为269例(53.0%),294例(57.9%)有过自杀观念,55例(10.8%)曾有自杀行为.45例(8.9%)伴精神病性症状.HAMD量表总分平均为(32.6±7.7)分;HAMA量表平均为(21.0±7.3)分,其中78.5%患者大于14分.抑郁症患者焦虑障碍的共病发生率为68.9%(350例),16.7%共病多种焦虑障碍.焦虑障碍种类分布以广泛性焦虑障碍为主,为56.1%.焦虑对抑郁症的临床严重程度有显著统计学意义,但自杀观念和自杀行为在共病与非共病之间未见统计学意义.36.0%患者同时伴有躯体疾病.结论 抑郁症与焦虑共病在临床上是常见的现象,合并的焦虑障碍以广泛性焦虑障碍为主,1/3的患者合并躯体疾病,应引起临床医生重视.