Panic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia.

We compared the neural activations of 72 patients suffering from panic disorder with agoraphobia with 72 matched healthy control subjects in a 3-T fMRI study. To isolate agoraphobia-specific alterations we tested the effects of the anticipation and perception of an agoraphobia-specific stimulus set. During fMRI, 48 agoraphobia-specific and 48 neutral pictures were randomly presented with and without anticipatory stimulus indicating the content of the subsequent pictures (Westphal paradigm).

During the anticipation of agoraphobia-specific pictures, stronger activations were found in the bilateral ventral striatum and left insula in patients compared with controls. There were no group differences during the perception phase of agoraphobia-specific pictures.

This study revealed stronger region-specific activations in patients suffering from panic disorder with agoraphobia in anticipation of agoraphobia-specific stimuli. Patients seem to process these stimuli more intensively based on individual salience. Hyperactivation of the ventral striatum and insula when anticipating agoraphobia-specific situations might be a central neurofunctional correlate of agoraphobia. Knowledge about the neural correlates of anticipatory and perceptual processes regarding agoraphobic situations will help to optimize and evaluate treatments, such as exposure therapy, in patients with panic disorder and agoraphobia.

Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic disorder with high rates of psychosis and other psychopathologies, but few studies discuss treatment. Our aim was to characterize the prevalence and treatment of major psychiatric illnesses in a well-characterized sample of individuals with 22q11DS.

This was a cross-sectional study of 112 individuals aged 8 to 45 years with a confirmed diagnosis of 22q11DS. Each participant was administered a modified Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) and the Structured Interview for Prodromal Syndromes (SIPS). Phenotypes assessed were threshold and subthreshold psychosis, depression, mania, generalized and separation anxiety, obsessions/compulsions, inattention/hyperactivity and substance use. Histories of mental health care and current psychotropic treatment were obtained.

Psychopathology was common, with 79% of individuals meeting diagnostic criteria for a disorder at the time of assessment. Diagnoses of psychosis were made in 11% of cases, attenuated positive symptom syndrome (APS) in 21%, and 47% experienced significant subthreshold symptoms. Peak occurrence of psychosis risk was during adolescence (62% of those aged 12–17 years). Criteria for a mood disorder were met by 14%, for anxiety disorder 34% and for attention deficit hyperactivity disorder (ADHD) 31%. Mental health care had been received by 63% of individuals in their lifetime, but only 40% continued therapy and 39% used psychotropics. Antipsychotics were used by 42% of participants with psychosis and none of the participants with APS. Half of those at risk for psychosis were receiving no mental health care.

Psychopathology is common in 22q11DS but is not adequately treated or clinically followed. Particular attention should be paid to subthreshold psychotic symptoms, especially in adolescents.

Deep brain stimulation (DBS) is a promising new treatment for patients with treatment-refractory obsessive–compulsive disorder (OCD). However, since most DBS patients only show a partial response, the treatment still needs to be improved. In this study we hypothesized that cognitive–behavioural therapy (CBT) could optimize the post-operative management in DBS and we evaluated the efficacy of CBT as augmentation to DBS targeted at the nucleus accumbens.

A total of 16 patients with treatment-refractory OCD were treated with DBS targeted at the nucleus accumbens. After stabilization of decline in OCD symptoms, a standardized 24-week CBT treatment programme was added to DBS in an open-phase trial of 8 months. Changes in obsessive–compulsive, anxiety and depressive symptoms were evaluated using the Yale–Brown Obsessive Compulsive Scale, Hamilton Anxiety Scale and Hamilton Rating Scale for Depression.

Following the addition of CBT to DBS, a significant decrease in obsessive–compulsive symptoms was observed, but not in anxiety and depressive symptoms. In a subsequent double-blind phase, in which stimulation was discontinued, OCD symptoms returned to baseline (relapse) and anxiety and depressive symptoms worsened (rebound) compared with baseline.

The results of this explorative study suggest that a combined treatment of accumbens DBS and CBT may be optimal for improving obsessive–compulsive symptoms in treatment-refractory OCD. However, a subsequent randomized controlled trial is necessary to draw firm conclusions. It seems that DBS results in affective changes that may be required to enable response prevention in CBT. This may indicate that DBS and CBT act as two complementary treatments.

Structural models of emotional disorders propose that anxiety disorders can be classified into fear and distress disorders. Sources of evidence for this distinction come from genetic, self-report and neurophysiological data from adults. The present study examined whether this distinction relates to cognitive processes, indexed by attention bias towards threat, which is thought to cause and maintain anxiety disorders.

Diagnostic and attention bias data were analysed from 435 children between 5 and 13 years of age; 158 had principal fear disorder (specific phobia, social phobia or separation anxiety disorder), 75 had principal distress disorder (generalized anxiety disorder, GAD) and 202 had no psychiatric disorder. Anxious children were a clinic-based treatment-seeking sample. Attention bias was assessed on a visual-probe task with angry, neutral and happy faces.

Compared to healthy controls, children with principal distress disorder (GAD) showed a significant bias towards threat relative to neutral faces whereas children with principal fear disorder showed an attention bias away from threat relative to neutral faces. Overall, children displayed an attention bias towards happy faces, irrespective of diagnostic group.

Our findings support the distinction between fear and distress disorders, and extend empirically derived structural models of emotional disorders to threat processing in childhood, when many anxiety disorders begin and predict lifetime impairment.

Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period.

Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model.

The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA.

Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic–environment correlation (rGE) and interaction (G × E) analyses.

Individuals with borderline personality disorder (BPD) frequently display co-morbid mental disorders. These disorders include ‘internalizing’ disorders (such as major depressive disorder and anxiety disorders) and ‘externalizing’ disorders (such as substance use disorders and antisocial personality disorder). It is hypothesized that these disorders may arise from latent ‘internalizing’ and ‘externalizing’ liability factors. Factor analytic studies suggest that internalizing and externalizing factors both contribute to BPD, but the extent to which such contributions are familial is unknown.

Participants were 368 probands (132 with BPD; 134 without BPD; and 102 with major depressive disorder) and 885 siblings and parents of probands. Participants were administered the Diagnostic Interview for DSM-IV Personality Disorders, the Revised Diagnostic Interview for Borderlines, and the Structured Clinical Interview for DSM-IV.

On confirmatory factor analysis of within-person associations of disorders, BPD loaded moderately on internalizing (factor loading 0.53, s.e. = 0.10, p < 0.001) and externalizing latent variables (0.48, s.e. = 0.10, p < 0.001). Within-family associations were assessed using structural equation models of familial and non-familial factors for BPD, internalizing disorders, and externalizing disorders. In a Cholesky decomposition model, 84% (s.e. = 17%, p < 0.001) of the association of BPD with internalizing and externalizing factors was accounted for by familial contributions.

Familial internalizing and externalizing liability factors are both associated with, and therefore may mutually contribute to, BPD. These familial contributions account largely for the pattern of co-morbidity between BPD and internalizing and externalizing disorders.

Hippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis.

Magnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor.

BHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI.

BHI occurs in a minority of patients following their first psychotic episode and is associated with good outcome across clinical, functional and cognitive domains.

Twin studies of veterans and adults suggest that approximately 30–46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure.

The sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male–male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure.

Biometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure.

Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

What determines inter-individual variability to impairments in behavioural control that may underlie road-traffic accidents, and impulsive and violent behaviours occurring under the influence of cannabis, the most widely used illicit drug worldwide?

Employing a double-blind, repeated-measures design, we investigated the genetic and neural basis of variable sensitivity to cannabis-induced behavioural dyscontrol in healthy occasional cannabis users. Acute oral challenge with placebo or Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, was combined with functional magnetic resonance imaging, while participants performed a response inhibition task that involved inhibiting a pre-potent motor response. They were genotyped for rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1) gene.

Errors of inhibition were significantly (p = 0.008) increased following administration of THC in carriers of the A allele, but not in G allele homozygotes of the AKT1 rs1130233 SNP. The A allele carriers also displayed attenuation of left inferior frontal response with THC evident in the sample as a whole, while there was a modest enhancement of inferior frontal activation in the G homozygotes. There was a direct relationship (r = − 0.327, p = 0.045) between the behavioural effect of THC and its physiological effect in the inferior frontal gyrus, where AKT1 genotype modulated the effect of THC.

These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.

Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits.

We assessed 704 subjects (age 6–12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90), Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n = 39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed–accuracy trade-off and encoding/motor function along with variability parameters.

Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP.

Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.

Numerous studies have supported an association between maternal depression and child psychiatric outcomes, but few have controlled for the confounding effects of both maternal and offspring co-morbidity. Thus, it remains unclear whether the correspondence between maternal and offspring depressive and anxiety disorders is better explained by associations between shared features of maternal and offspring internalizing disorders or by specific effects exerted by unique aspects of individual disorders.

Pairs of mothers and offspring overselected for maternal depression (n = 815) were assessed at offspring age 15 years for anxiety and depressive disorders; 705 completed a follow-up at offspring age 20 years. For both mothers and offspring, structural equation modeling was used to distinguish transdiagnostic internalizing pathology – representing the overlap among all depressive and anxiety disorders – from diagnosis-specific forms of pathology. To discriminate between general versus specific pathways of intergenerational transmission of psychopathology, we examined (a) the general association between the maternal and offspring internalizing factors and (b) the correlations between maternal and offspring diagnosis-specific pathology for each disorder.

For mothers and offspring, a unidimensional latent variable model provided the best fit to the correlations among depressive and anxiety disorders. The maternal transdiagnostic internalizing factor strongly predicted the corresponding factor among offspring. In addition, the unique component of post-traumatic stress disorder among offspring was significantly related to the analogous unique component among mothers, but specific components of other maternal disorders, including depression, did not predict corresponding offspring pathology.

Results suggest that intergenerational transmission of internalizing disorders is largely non-specific.

Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients.

The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls.

Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.

The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.

Available research has suggested that affiliation with prosocial peers reduces child and adolescent antisocial behavior. However, the etiologic mechanisms driving this association remain unclear. The current study sought to evaluate whether this association takes the form of a gene–environment interaction (G × E) in which prosocial peer affiliation acts to reduce the consequences of genetic risk for non-aggressive antisocial behavior during childhood.

Our sample consisted of 500 twin pairs aged 6–10 years from the Michigan State University Twin Registry (MSUTR).

The results robustly support moderation by prosocial peer affiliation. Genetic influences on non-aggressive antisocial behavior were observed to be several times larger in those with lower levels of prosocial peer affiliation than in those with higher levels of prosocial peer affiliation. This pattern of results persisted even after controlling for gene–environment correlations and deviant peer affiliation, and when restricting our analyses to those twins who shared all or nearly all of their friends.

Such findings not only suggest that prosocial peer affiliation moderates genetic influences on non-aggressive antisocial behaviors during childhood but also provide support for the theoretical notion that protective environmental experiences may exert their influence by promoting resilience to genetic risk.

The aetiology of depression is multifactorial, with biological, cognitive and environmental factors across the life course influencing risk of a depressive episode. There is inconsistent evidence linking early life development and later depression. The aim of this study was to investigate relationships between low birthweight (LBW), infant neurodevelopment, and acute and chronic stress as components in pathways to depression in adulthood.

The sample included 4627 members of the National Survey of Health and Development (NSHD; the 1946 British birth cohort). Weight at birth, age of developmental milestones, economic deprivation in early childhood, acute stressors in childhood and adulthood, and socio-economic status (SES) in adulthood were assessed for their direct and indirect effects on adolescent (ages 13 and 15 years) and adult (ages 36, 43 and 53 years) measures of depressive symptoms in a structural equation modelling (SEM) framework. A structural equation model developed to incorporate all variables exhibited excellent model fit according to several indices.

The path of prediction from birthweight to age of developmental milestones to adolescent depression/anxiety to adult depression/anxiety was significant (p < 0.001). Notably, direct paths from birthweight (p = 0.25) and age of developmental milestones (p = 0.23) to adult depression were not significant. Childhood deprivation and stressors had important direct and indirect effects on depression. Stressors in adulthood were strongly associated with adult depression.

Depression in adulthood is influenced by an accumulation of stressors across the life course, including many that originate in the first years of life. Effects of early-life development on mental health appear by adolescence.

DSM-IV specifies a hierarchal diagnostic structure such that an oppositional defiant disorder (ODD) diagnosis is applied only if criteria are not met for conduct disorder (CD). Genetic studies of ODD and CD support a combination of shared genetic and environmental influences but largely ignore the imposed diagnostic structure.

We examined whether ODD and CD share an underlying etiology while accounting for DSM-IV diagnostic specifications. Data from 1446 female twin pairs, aged 11–19 years, were fitted to two-stage models adhering to the DSM-IV diagnostic hierarchy.

The models suggested that DSM-IV ODD–CD covariation is attributed largely to shared genetic influences.

This is the first study, to our knowledge, to examine genetic and environmental overlap among these disorders while maintaining a DSM-IV hierarchical structure. The findings reflect primarily shared genetic influences and specific (i.e. uncorrelated) shared/familial environmental effects on these DSM-IV-defined behaviors. These results have implications for how best to define CD and ODD for future genetically informed analyses.

Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations.

Twenty-two smokers diagnosed with schizophrenia and 23 control smokers were assessed for smoking-related attentional bias using a modified Stroop task. Craving, nicotine dependence, smoking behaviour and positive and negative symptoms of schizophrenia were also recorded.

Both groups showed similar craving scores and smoking behaviour according to self-report and expired carbon monoxide (CO), although the patient group had higher nicotine dependence scores. Attentional bias, as evidenced by significant interference from smoking-related words on the modified Stroop task, was similar in both groups and correlated with CO levels. Attentional bias was positively related to severity of delusions but not hallucinations or other symptoms in the schizophrenia group.

This study supports the hypothesis that the development of delusions and the incentive motivational aspects of smoking may share a common biological substrate. These findings may offer some explanation for the elevated rates of smoking and other drug use in people with psychotic illness.

Oxytocin (OT) is associated with our ability to empathize and has been shown to play a major role in mediating social behaviors within the context of intergroup dynamics. Schizophrenia is associated with impaired empathy, and with a dysfunctional oxytocinergic system. The effect of OT on the empathic responses of patients with schizophrenia within the context of intergroup relationships has not been studied. The present study examined the effect of OT on the patients' empathic responses to pain experienced by in-group, conflictual out-group and neutral out-group members.

In a double-blind, placebo-controlled, within-subject cross-over design, the responses on the Pain Evaluation Task of 28 male patients with schizophrenia were compared to 27 healthy male controls. All participants received a single intranasal dose of 24 IU OT or placebo, 1 week apart.

OT induced an empathy bias in the healthy controls towards the conflictual out-group members. Although this effect was absent in the patient group, OT seems to heighten an empathic bias in the patient group towards the in-group members when rating non-painful stimuli.

The study demonstrates that the administration of OT can result in empathic bias towards adversary out-group members in healthy controls but not in patients with schizophrenia. However, the OT-induced bias in both the patients (in the no-pain condition towards the in-group members) and the healthy controls (in the no-pain and pain conditions towards the adversary out-group) suggests that OT enhances the distinction between conflictual in-group and out-group members.

The mechanisms by which childhood abuse and family history of suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still unknown. Impulsive aggression may play an intermediate role. We investigated whether greater scores for aggression and impulsivity might be associated with the effects of FHS and/or childhood abuse on the severity of suicidal behavior.

We examined the scores of three scales measuring impulsive aggression in a sample of 696 suicide attempters. We compared the highest and lowest scores with regard to reports of childhood abuse and FHS using adjusted multinomial regression models. Genetic polymorphisms of the serotonergic system known to be associated with impulsive aggression were also analyzed.

Patients with high impulsive aggressive scores showed significant differences in sociodemographic, clinical and suicidal features compared with patients with low impulsive aggressive scores. Adjusted results showed that combinations of some types of childhood abuse and FHS, particularly emotional abuse and emotional neglect, are associated with high impulsivity and hostility scores. The SS genotype of the serotonin transporter gene (5-HTTLPR) was associated with high levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR) 5.55, 95% confidence interval (CI) 1.75–17.5] or physical abuse (OR 5.03, 95% CI 1.50–16.9) in their childhood.

Our results support the role of impulsive aggression as one of the links that may connect childhood abuse and FHS with severity of suicidal behavior.

The neurocognitive deficits and other correlates of problem gambling are also observable in individuals with lower cognitive abilities, suggesting that a low IQ may be a determinant of problem gambling. There has been very little research into this possibility. This study aimed to investigate the characteristics associated with problem gambling in a large population-based study in England, with a particular focus on IQ.

The Adult Psychiatric Morbidity Survey (APMS) 2007 comprised detailed interviews with 7403 individuals living in private households in England. Problem gambling was ascertained using a questionnaire based on DSM-IV criteria. Verbal IQ was estimated using the National Adult Reading Test (NART). Confounders included socio-economic and demographic factors, common mental disorders, impulsivity, smoking, and hazardous drug and alcohol use.

More than two-thirds of the population reported engaging in some form of gambling in the previous year, but problem gambling was rare [prevalence 0.7%, 95% confidence interval (CI) 0.5–1.0]. The odds of problem gambling doubled with each standard deviation drop in estimated verbal IQ [adjusted odds ratio (OR) 2.1, 95% CI 1.3–3.4, p = 0.003], after adjusting for other characteristics associated with problem gambling including age, sex, socio-economic factors, drug and alcohol dependence, smoking, impulsivity and common mental disorders. There was no strong relationship observed between IQ and non-problem gambling.

People with lower IQs may be at a higher risk of problem gambling. Further work is required to replicate and study the mechanisms behind these findings, and may aid the understanding of problem gambling and inform preventative measures and interventions.

Brain structure alterations have been reported in anorexia nervosa, but findings have been inconsistent. This may be due to inadequate sample size, sample heterogeneity or differences in methodology.

High resolution magnetic resonance images were acquired of 33 adult participants with anorexia nervosa and 33 healthy participants, the largest study sample to date, in order to assess whole-brain volume, ventricular cerebrospinal fluid, white matter and grey matter volume. Voxel-based morphometry was conducted to assess regional grey matter volume. Levels of depression, anxiety, obsessionality and eating disorder-related symptoms were measured and used to explore correlations with brain structure.

Participants with anorexia nervosa had smaller brain volumes as well as a global decrease in grey matter volume with ventricular enlargement. Voxel-based morphometry revealed a decrease in grey matter volume spanning across the cerebellum, temporal, frontal and occipital lobes. A correlation was found between grey matter volume loss and duration of illness in the cerebellum and mesencephalon. No correlations were found with clinical measures.

Findings are in accordance with several previous studies on brain structure and match functional studies that have assessed the symptomatology of anorexia nervosa, such as body image distortion and cognitive bias to food. The correlation with duration of illness supports the implication of cerebellar atrophy in the maintenance of low weight and disrupted eating behaviour and illustrates its role in the chronic phase of anorexia nervosa. The lack of other correlations suggests that these findings are not related to the presence of co-morbid disorders.