Smoking cessation improves physical health but it has been suggested that in vulnerable individuals it may worsen mental health. This study aimed to identify the short- and longer-term effects of stopping smoking on depression and anxiety in the general population and in those with a history of these disorders.

Sociodemographic and smoking characteristics, and mental and physical health were assessed using established measures in the ATTEMPT cohort, an international longitudinal study of smokers (n = 3645). Smokers who had stopped for at least 3 months or less than 3 months at the 12-month follow-up were compared with current smokers (n = 1640).

At follow-up, 9.7% [95% confidence interval (CI) 8.3–11.2] of smokers had stopped for less than 3 months and 7.5% (95% CI 6.3–8.9) for at least 3 months. Compared with current smokers, prevalence of depression prescriptions obtained in the last 2 weeks was lower for those who had stopped for less than 3 months [odds ratio (OR) 0.37, 95% CI 0.14–0.96] or at least 3 months (OR 0.25, 95% CI 0.06–0.94) after adjusting for baseline prescription levels and confounding variables. Adjusted prevalence of recent depression symptoms was also lower for ex-smokers who had stopped for less than 3 months (OR 0.34, 95% CI 0.15–0.78) or at least 3 months (OR 0.24, 95% CI 0.09–0.67) than among continuing smokers. There was no change in anxiety measures in the general population or any increase in anxiety or depression symptoms in ex-smokers with a past history of these conditions.

Smoking cessation does not appear to be associated with an increase in anxiety or depression and may lead to a reduced incidence of depression.

This study surveyed the characteristics of white matter (WM) micro-integrity in patients who were diagnosed with major depressive disorder (MDD) without co-morbidities.

A total of 44 patients with MDD and 27 normal controls were enrolled in our study. Diffusion tensor imaging images of patients and controls were pre-processed and analysed to estimate differences in WM micro-integrity between patients and controls by performing comparisons of the values obtained from fractional anisotropy (FA). FA outputs of patients and controls were compared by a non-parametric permutation-based method with global brain volume, age and gender as covariates. In addition, the between-group differences of radial diffusivity (RD) and axial diffusivity (AD) were assessed to explain the alterations in FA values. Correlations between clinical variables (such as depression severity, anxiety severity, illness duration) and FA values were also estimated in each group and across both groups.

The patients with MDD had significantly lower FA values than the controls, for the left superior longitudinal fasciculus (SLF) and the right anterior thalamic radiation (ATR). The reductions in FA values occurred in combination with elevated RD values in the bilateral SLF and decreased AD values in the bilateral ATR. FA values were negatively correlated with depression severity in the SLF and with illness duration in the right SLF and ATR.

MDD patients had significant alterations in the WM micro-integrity of the left SLF and the right ATR.

Longitudinal studies reporting the association between cannabis use and developing depression provide mixed results. The objective of this study was to establish the extent to which different patterns of use of cannabis are associated with the development of depression using meta-analysis of longitudinal studies.

Peer-reviewed publications reporting the risk of developing depression in cannabis users were located using searches of EMBASE, Medline, PsychINFO and ISI Web of Science. Only longitudinal studies that controlled for depression at baseline were included. Data on several study characteristics, including measures of cannabis use, measures of depression and control variables, were extracted. Odds ratios (ORs) were extracted by age and length of follow-up.

After screening for 4764 articles, 57 articles were selected for full-text review, of which 14 were included in the quantitative analysis (total number of subjects = 76058). The OR for cannabis users developing depression compared with controls was 1.17 [95% confidence interval (CI) 1.05–1.30]. The OR for heavy cannabis users developing depression was 1.62 (95% CI 1.21–2.16), compared with non-users or light users. Meta-regression revealed no significant differences in effect based on age of subjects and marginal difference in effect based on length of follow-up in the individual studies. There was large heterogeneity in the number and type of control variables in the different studies.

Cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders. There is need for further longitudinal exploration of the association between cannabis use and developing depression, particularly taking into account cumulative exposure to cannabis and potentially significant confounding factors.

Relatively lower executive functioning is characteristic of individuals with schizophrenia. As low socio-economic status (SES) early in life (i.e. parent SES) has been linked with lower executive skills in healthy children, we hypothesized that parental SES (pSES) would be more strongly related to executive functioning in individuals with schizophrenia than in controls and have a greater impact on prefrontal cortical morphology.

Healthy controls (n = 125) and individuals with schizophrenia (n = 102) completed tests assessing executive functioning and intelligence. The groups were matched on pSES, which was evaluated with the Hollingshead–Redlich scale. A principal components analysis (PCA) was conducted on 10 variables from six executive tests, yielding three specific components (fluency, planning and response inhibition). Voxel-based morphometry (VBM) was used to evaluate effects of pSES on gray matter (GM) concentration.

Lower pSES was associated with lower scores across the three executive functioning components, and a significant group by pSES interaction was observed such that low pSES, in particular, affected individuals with schizophrenia. These effects remained significant when intellectual ability, education and self-SES (sSES) were added as covariates. VBM revealed that lower pSES was associated with reduced GM volume in several anterior brain regions, especially the superior frontal gyrus, in patients but not in controls.

These findings suggest that individuals with schizophrenia may be particularly vulnerable to the adverse impact of low pSES, in terms of both lower executive skills and reduced anterior GM volumes.

Anxiety disorders are associated with substantial functional limitations but the course of functioning following symptom remission remains largely unknown.

Using data from the Netherlands Study of Depression and Anxiety (NESDA), we examined the 2-year trajectories of functioning in participants with chronic (n = 586) or remitting anxiety disorders (n = 385) and in healthy controls (n = 585). In participants with remitting anxiety disorders, we identified predictors of functioning from among sociodemographic, clinical and vulnerability variables. Data were analysed using linear mixed models (LMMs). Functioning was assessed with the World Health Organization Disability Assessment Schedule II (WHO DAS II).

At baseline, participants with remitting anxiety disorders functioned significantly better than those with chronic anxiety disorders, but significantly worse than controls. In both anxiety disorder groups, most impairment was reported in social functioning, occupational functioning and cognition. During the follow-up, functioning improved in both groups, probably due to treatments received. Participants who achieved symptom remission experienced moderate improvements in social functioning and cognition but not in occupational functioning. Of those who remitted, 45.8% reported functioning scores similar to healthy controls whereas 28.5% still functioned at the level of those with chronic anxiety disorders. Worse functioning was predicted by severe anxiety disorders, use of psychological treatment, co-morbid depressive disorders and maladaptive personality traits.

In anxiety disorders, symptom remission is accompanied by improvements in functioning but significant functional impairments may persist because of co-morbid disorders, lower functioning prior to the onset of the anxiety disorder or residual subthreshold anxiety symptoms.

There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.

The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.

The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.

Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.

In women, anxiety symptoms are common and increase during midlife, but little is known about whether these symptoms predict onsets of major depressive disorder (MDD) episodes. We examined whether anxiety symptoms are associated with subsequent episodes of MDD in midlife African-American and Caucasian women, and whether they confer a different risk for first versus recurrent MDD episodes.

A longitudinal analysis was conducted using 12 years of data from the Study of Women's Health Across the Nation (SWAN) Mental Health Study (MHS). The baseline sample comprised 425 Caucasian (n = 278) and African American (n = 147) community-dwelling women, aged 46.1 ± 2.5 years. Anxiety symptoms measured annually using a self-report questionnaire were examined in relation to MDD episodes in the subsequent year, assessed with the SCID. Multivariable models were estimated with random effects logistic regression.

Higher anxiety symptoms scores were associated with a significantly higher adjusted odds of developing an episode of MDD at the subsequent annual visit [odds ratio (OR) 1.47, p = 0.01], specifically for a recurrent episode (OR 1.49, p = 0.03) but non-significant for a first episode (OR 1.32, p = 0.27). There were no significant racial effects in the association between anxiety symptoms and subsequent MDD episodes.

Anxiety symptoms often precede MDD and may increase the vulnerability of midlife women to depressive episodes, particularly recurrences. Women with anxiety symptoms should be monitored clinically during the ensuing year for the development of an MDD episode.

Prior research with racially/ethnically homogeneous samples has demonstrated widespread co-occurrence of psychotic experiences (PEs) and common mental health conditions, particularly multi-morbidity, suggesting that psychosis may be related to the overall severity of psychiatric disorder rather than any specific subtype. In this study we aimed to examine whether PEs are associated with the presence of specific disorders or multi-morbidity of co-occurring disorders across four large racially/ethnically diverse samples of adults in the USA.

Data were drawn from the National Comorbidity Survey Replication (NCS-R), the National Survey of American Life (NSAL) and separately from the Asian and Latino subsamples of the National Latino and Asian American Study (NLAAS). Logistic regression models were used to examine the relationship between PEs and individual subtypes of DSM-IV disorder, and to test for a linear dose–response relationship between the number of subtypes and PEs.

Prevalence of PEs was moderately greater among individuals with each subtype of disorder in each data set [odds ratios (ORs) 1.8–3.8], although associations were only variably significant when controlling for clinical and demographic variables. However, the sum of disorder subtypes was related to odds for PEs in a linear dose–response fashion across all four samples.

PEs are related primarily to the extent or severity of psychiatric illness, as indicated by the presence of multiple psychiatric disorders, rather than to any particular subtype of disorder in these data. This relationship applies to the general population and across diverse racial/ethnic groups.

Using three independent methods, prior studies in Swedish sibling pairs indicate that environmental factors contribute substantially to familial aggregation for drug abuse (DA). Could we replicate these results in cousin pairs?

Using multiple Swedish public databases (1964–2011), we defined DA using medical, legal or pharmacy registry records and examined concordance in full cousin pairs as a function of age differences, younger–older relationships and geographical proximity while growing up.

Replicating prior results in siblings, cousin pairs were significantly more similar in their history of DA if they were (i) closer versus more distant in age and (ii) grew up in high versus low geographical proximity to one another. Furthermore, controlling for background factors, having an older cousin with DA conveys a greater risk for DA than having a younger drug-abusing cousin. The greater transmission of DA from older to younger versus younger to older cousin was more prominent in pairs who grew up close to one another. In age difference and geographical proximity analyses, effects were consistently strongest in male–male cousin pairs. In analyses of older → younger versus younger → older transmission, effects were stronger in male–male and male–female than in female–female or female–male relative pairs.

In accord with prior results in siblings, environmental factors contribute substantially to the familial aggregation of DA in cousins and these effects are, in general, stronger in males than in females.

Few studies have been published on the association between mental disorders and violence based on general population studies. Here we focus on different types of violence, adjusting for violent victimization and taking account of the limitations of previous population studies.

Data were used from the first two waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face-to-face survey of the general population aged 18–64 years (n = 6646). Violence was differentiated into physical and psychological violence against intimate partner(s), children or any person(s) in general. DSM-IV diagnoses were assessed with the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0).

Psychological violence occurs considerably more frequently than physical violence, but both showed almost identical associations with mental disorders. After adjustment for sociodemographic characteristics, most of the main categories of common mental disorders were associated with violence. The strongest associations were found for externalizing disorders (substance use, impulse-control, antisocial personality disorder). After additional adjustment for violent victimization, negative life events and social support, most diagnostic correlates lost their significance whereas substance use (in particular alcohol) disorders were still associated with most types of violence.

The increased risk of violent offending among people with common mental disorders, other than substance use disorders, can be attributed to factors other than their mental illness.

Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging.

A total of 61 youth (9–17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy.

There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n = 22) and low and decreasing (LowD; n = 39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p < 0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's < 0.001, corrected).

Patterns of function in lateral prefrontal cortical–amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.

Although impaired recognition of affective facial expressions has been conclusively linked to antisocial behavior, little is known about the modifiability of this deficit. This study investigated whether and under which circumstances the proposed perceptual insensitivity can be addressed with a brief implicit training approach.

Facial affect recognition was assessed with an animated morph task, in which the participants (44 male incarcerated violent offenders and 43 matched controls) identified the onset of emotional expressions in animated morph clips that gradually changed from neutral to one of the six basic emotions. Half of the offenders were then implicitly trained to direct attention to salient face regions (attention training, AT) using a modified dot-probe task. The other half underwent the same protocol but the intensity level of the presented expressions was additionally manipulated over the course of training sessions (sensitivity to emotional expressions training, SEE training). Subsequently, participants were reassessed with the animated morph task.

Facial affect recognition was significantly impaired in violent offenders as compared with controls. Further, our results indicate that only the SEE training group exhibited a pronounced improvement in emotion recognition.

We demonstrated for the first time that perceptual insensitivity to facial affect can be addressed by an implicit training that directs attention to salient regions of a face and gradually decreases the intensity of the emotional expression. Future studies should focus on the potential of this intervention to effectively increase empathy and inhibit violent behavior in antisocial individuals.

Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.

Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).

In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.

This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

The DSM-5 alcohol use disorder (AUD) criteria proposal contains 11 criteria that include most of the DSM-IV abuse and dependence criteria plus craving. The aims of the current study in a large and international alcohol-consuming sample were to confirm the dimensionality of the DSM-5 AUD criteria and to differentiate grades of severity of DSM-5 AUD in subjects who pass the proposed DSM-5 diagnostic threshold of two criteria.

We used the World Health Organization (WHO)/International Society on Biomedical Research on Alcoholism (ISBRA) Study on State and Trait Markers of Alcohol Use and Dependence dataset. Subjects included in the analyses were aged ⩾18 years and were recruited in five countries: Australia, Brazil, Canada, Finland and Japan. Assessment of AUD and additional characteristics was conducted using an adapted version of the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS). Dimensionality of the DSM-5 criteria was evaluated using factor analysis and item response theory (IRT) models. The IRT results led to the classification of AUD patients into three severity groups. External validators were used to differentiate statistically across subgroups.

A total of 1424 currently drinking individuals were included in the analyses. Factor and IRT analyses confirmed the dimensional structure of DSM-5 AUD criteria. More than 99% of the subjects could be allocated to one of the suggested severity subgroups. The magnitude of the external validators differed significantly across the severity groups.

The results confirm the dimensional structure of the proposed DSM-5 AUD criteria. The suggested stages of severity (mild, moderate and severe) may be useful to clinicians by grouping individuals not only in the mild but also in the moderate to severe spectrum of DSM-5 AUD.

Emotional and behavioral problems are commonly associated with substance use in adolescence but it is unclear whether substance use precedes or follows mental health problems. The aim was to investigate longitudinal associations between externalizing and internalizing psychopathology and substance use in a prospective population study design.

The sample was the Northern Finland Birth Cohort 1986 Study (NFBC 1986; n = 6349; 3103 males). Externalizing and internalizing mental health problems were assessed at age 8 years (Rutter scales), substance use and externalizing and internalizing problems [Youth Self-Report (YSR)] at age 15–16 years, and hospital diagnoses for internalizing disorders (age 25) and criminal offences (age 20) from nationwide registers in adulthood.

Externalizing problems at age 8 were associated with later substance use. After adjustment for sociodemographic factors, parental alcohol use and psychiatric disorders, and earlier externalizing and internalizing problems, substance use predicted criminality, especially among males, with the highest odds ratio (OR) for cannabis use [adjusted OR 6.2, 95% confidence interval (CI) 3.1–12.7]. Early internalizing problems were not a risk for later substance use. Female adolescent cannabis (OR 3.2, 95% CI 1.4–7.3) and alcohol (OR 2.1, 95% CI 1.1–4.2) use predicted internalizing disorders in adulthood.

Externalizing problems precede adolescent substance use in both genders, whereas, among boys, substance use also precedes criminal offences. Internalizing problems may follow substance use in females. These associations were robust even when taking into account previous mental health problems.

Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.

To examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants.

The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression.

Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

Previous research has demonstrated an association between low motivation to change and an unfavorable treatment outcome in patients with an eating disorder. Consequently, various studies have examined the effects of motivational enhancement therapy (MET) on motivation to change and treatment outcome in eating disorders. In each of these studies, MET was administered in a face-to-face setting. However, because of its anonymity and ease of access, the internet provides several advantages as the format for such an intervention. Therefore, the current study investigated the effects of an internet-based program (‘ESS-KIMO’) to enhance motivation to change in eating disorders.

In total, 212 females were accepted for participation and assigned randomly to the intervention condition (n = 103) or waiting-list control condition (n = 109). The intervention consisted of six online MET sessions. Before and after the intervention or waiting period respectively, participants completed the Eating Disorder Examination Questionnaire (EDE-Q), the Stages of Change Questionnaire for Eating Disorders (SOCQ-ED), the Pros and Cons of Eating Disorders Scale (P-CED), the Self-Efficacy Scale (SES), and the Rosenberg Self-Esteem Scale (RSES). A total of 125 participants completed the assessment post-treatment. Completer analyses and intent-to-treat analyses were performed.

Significant time × group interactions were found, indicating a stronger increase in motivational aspects and self-esteem, in addition to a stronger symptom reduction on some measures from pre- to post-treatment in the intervention group compared to the control group.

Internet-based approaches can be considered as useful for enhancing motivation to change in eating disorders and for yielding initial symptomatic improvement.

Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.

In total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.

Increased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1–3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.

These data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.

Previous studies have found that patients with schizophrenia are more likely to be violent than the general population. The aim of this study was to investigate the association between schizophrenia and violent crime in the Israeli population.

Using the Israeli Psychiatric Hospitalization Case Registry we identified 3187 patients with a discharge diagnosis of schizophrenia. For each proband we identified parents and siblings, and gender- and age-matched controls for patients, parents and siblings. Information on violent crimes was obtained from police records.

Patients with schizophrenia were at increased risk for violent crimes compared with controls [odds ratio (OR) 4.3, 95% confidence interval (CI) 3.8–4.9], especially women (OR 9.9, 95% CI 6.2–15.7). Risk for violent crimes was higher among patients with co-morbid substance misuse than in patients without such co-morbidity (OR 5.1, 95% CI 4.2–6.3).

The results of this study suggest that increased risk of violence is part of the clinical picture of schizophrenia and needs to be recognized as a legitimate, essential, aspect of clinical management.

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.