The role played by anxiety in the history of psychiatric epidemiology has not been well recognized. Such lack of understanding retarded the incremental growth of psychiatric research in general populations. It seems useful to look back on this history while deliberations are being carried out about how anxiety will be presented in DSM-V.

Drawing on the literature and our own research, we examined work that was carried out during and after the Second World War by a Research Branch of the United States War Department, by the Stirling County Study, and by the Midtown Manhattan Study. The differential influences of Meyerian psychobiology and Freudian psychoanalysis are noted.

The instruments developed in the early epidemiologic endeavors used questions about nervousness, palpitations, sweating, trembling, shortness of breath, upset stomach, etc. These symptoms are important features of what the clinical literature called ‘manifest’, ‘free-floating’ or ‘chronic anxiety’. A useful descriptive name is ‘autonomic anxiety’.

Although not focusing on specific circumstances as in Panic and Phobic disorders, a non-specific form of autonomic anxiety is a common, disabling and usually chronic disorder that received empirical verification in studies of several community populations. It is suggested that two types of general anxiety may need to be recognized, one dominated by excessive worry and feelings of stress, as in the current DSM-IV definition of Generalized Anxiety Disorder (GAD), and another emphasizing frequent unexplainable autonomic fearfulness, as in the early epidemiologic studies.

Spontaneous movement disorders (SMDs), such as spontaneous dyskinesia and parkinsonism, have been described in patients with schizophrenia who have never been treated with antipsychotic medication. Their presence has been documented extensively in chronic schizophrenia but not at the time of illness onset.

We performed a systematic review of studies investigating spontaneous abnormal movements elicited on clinical examination in antipsychotic-naive patients with first-episode psychosis.

We identified a total of 13 studies. Findings suggest a spontaneous dyskinesia median rate of 9% and a spontaneous parkinsonism median rate of 17%. Information on akathisia and dystonia was limited. The presence of SMDs may be associated with negative symptoms and cognitive dysfunction.

These findings support the notion that spontaneous abnormal movements are part of a neurodysfunction intrinsic to the pathogenesis of schizophrenia. Future studies should further investigate the role of basal ganglia and extrapyramidal pathways in the pathophysiology of psychosis, with particular attention to treatment implications.

Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity.

Twin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA.

All three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity.

The findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.

Taxometric research on depression has yielded mixed results, with some studies supporting dimensional solutions and others supporting taxonic solutions. Although supplementary tests of construct validity might clarify these mixed findings, to date such analyses have not been reported. The present study represents a follow-up to our previous taxometric study of depression designed to evaluate the relative predictive validities of dimensional and categorical models of depression.

Two sets of dimensional and categorical models of depression were constructed from the depression items of the Composite International Diagnostic Interview: (1) empirically derived models obtained using latent structure analyses and (2) rationally selected models, including an additive depressive symptoms scale (dimensional) and DSM major depressive episodes (categorical). Both sets of dimensional and categorical models were compared in terms of their abilities to predict various clinically relevant outcomes (psychiatric diagnoses and impairment).

Factor analyses suggested a two-factor model (‘cognitive–affective’ and ‘somatic’ symptoms) and latent class analyses suggested a three-class model (‘severe depression’, ‘moderate depression’ and ‘cognitive–affective distress’). In predictive analyses that simultaneously included dimensional and categorical models as predictors, the dimensional models remained significant unique predictors of outcomes while the categorical models did not.

Both dimensional models provided superior predictive validity relative to their categorical counterparts. These results provide construct validity evidence for the dimensional findings from our previous taxometric study and thus inspire confidence in dimensional conceptualizations of depression. It remains for future research to evaluate the construct validity of the taxonic solutions reported in the literature.

Patients with major depressive disorder are found to show selective attention biases towards mood-congruent information. Although previous studies have identified various structural changes in the brains of these patients, it remains unclear whether the structural abnormalities are associated with these attention biases. In this study, we used voxel-based morphometry (VBM) to explore the structural correlates of attention biases towards depression-related stimuli.

Seventeen female patients with major depressive disorder and 17 female healthy controls, matched on age and intelligence, underwent magnetic resonance imaging (MRI). They also performed positive-priming (PP) and negative-priming (NP) tasks involving neutral and negative words that assessed selective attention biases. The reaction time (RT) to a target word that had been attended to or ignored in a preceding trial was measured on the PP and NP tasks respectively. The structural differences between the two groups were correlated with the indexes of attention biases towards the negative words.

The enhanced facilitation of attention to stimuli in the PP task by the negative valence was only found in the depressed patients, not in the healthy controls. Such attention biases towards negative stimuli were found to be associated with reduced gray-matter concentration (GMC) in the right superior frontal gyrus, the right anterior cingulate gyrus and the right fusiform gyrus. No differential effect in inhibition of attention towards negative stimuli in the NP task was found between the depressed patients and the healthy controls.

Specific structural abnormalities in depression are associated with their attention biases towards mood-congruent information.

Background. There is uncertainty about the diagnostic significance of specific symptoms of major depressive disorder (MDD). There is also interest in using one or two specific symptoms in the development of brief scales. Our aim was to elucidate the best possible specific symptoms that would assist in ruling in or ruling out a major depressive episode in a psychiatric out-patient setting.

A total of 1523 psychiatric out-patients were evaluated in the Methods to Improve Diagnostic Assessment and Services (MIDAS) project. The accuracy and added value of specific symptoms from a comprehensive item bank were compared against the Structured Clinical Interview for DSM-IV (SCID).

The prevalence of depression in our sample was 54.4%. In this high prevalence setting the optimum specific symptoms for ruling in MDD were psychomotor retardation, diminished interest/pleasure and indecisiveness. The optimum specific symptoms for ruling out MDD were the absence of depressed mood, the absence of diminished drive and the absence of loss of energy. However, some discriminatory items were relatively uncommon. Correcting for frequency, the most clinically valuable rule-in items were depressed mood, diminished interest/pleasure and diminished drive. The most clinically valuable rule-out items were depressed mood, diminished interest/pleasure and poor concentration.

The study supports the use of the questions endorsed by the two-item Patient Health Questionnaire (PHQ-2) with the additional consideration of the item diminished drive as a rule-in test and poor concentration as a rule-out test. The accuracy of these questions may be different in primary care studies where prevalence differs and when they are combined into multi-question tests or algorithmic models.

Risk for mood and anxiety disorders associated with US-nativity may vary across immigrant groups.

Using data from the National Epidemiological Study of Alcohol and Related Conditions (NESARC), we examined the association of lifetime risk for mood and anxiety disorders with US-nativity and age at immigration across seven subgroups of the US population defined by country or region of ancestral origin: Mexico, Puerto-Rico, Cuba, Central and South America, Western Europe, Eastern Europe, and Africa and the Caribbean. Discrete time survival models were used to compare lifetime risk between the US-born, immigrants who arrived in the USA prior to the age of 13 years and immigrants who arrived in the USA at the age of 13 years or older.

The association of risk for mood and anxiety disorders with US-nativity varies significantly across ancestral origin groups (p<0.001). Among people from Mexico, Eastern Europe, and Africa or the Caribbean, risk for disorders is lower relative to the US-born among immigrants who arrived at the age of 13 years or higher (odds ratios in the range 0.34–0.49) but not among immigrants who arrived prior to the age of 13 years. There is no association between US-nativity and risk for disorder among people from Western Europe and Puerto Rico.

Low risk among immigrants relative to the US-born is limited to groups among whom risk for mood and anxiety disorder is low in immigrants who spent their pre-adolescent years outside of the USA.

Vulnerability–stress models ascribe stress a pivotal role in the development of psychosis. However, moderating and mediating mechanisms translating stress into psychosis and the specificity of the association are not clearly established. It is hypothesized that stress will trigger paranoid ideation in vulnerable individuals through an increase in negative emotion.

Using a repeated-measures design, 64 healthy participants with varying levels of vulnerability [psychosis symptoms assessed by the Community Assessment of Psychic Experiences (CAPE)] were assigned to a stress and a non-stress condition in random order. Stress was induced by exposing participants to building-site noise (75 dB) applied concurrently with difficult knowledge questions. Symptoms of paranoia, depression and obsessive compulsive disorder (OCD) were assessed by state-adapted versions of clinical scales.

In the stress condition there was an increase in paranoia, depression and negative emotion. Multilevel linear modeling (MLM) revealed the increase in paranoia under stress to be moderated by the level of vulnerability and mediated by anxiety. Although participants generally showed an increase in anxiety under stress, anxiety was more strongly related to paranoia in participants with higher baseline symptomatology.

The results support and specify the role of emotional reactions to stressors on the pathway from vulnerability to psychosis and highlight the relevance of anxiety.

Previous studies investigating attentional biases in social anxiety disorder (SAD) have yielded mixed results. Recent event-related potential (ERP) studies using the dot-probe paradigm in non-anxious participants have shown that the P1 component is sensitive to visuospatial attention towards emotional faces. We used a dot-probe task in conjunction with high-density ERPs and source localization to investigate attentional biases in SAD.

Twelve SAD and 15 control participants performed a modified dot-probe task using angry–neutral and happy–neutral face pairs. The P1 component elicited by face pairs was analyzed to test the hypothesis that SAD participants would display early hypervigilance to threat-related cues. The P1 component to probes replacing angry, happy or neutral faces was used to evaluate whether SAD participants show either sustained hypervigilance or decreased visual processing of threat-related cues at later processing stages.

Compared to controls, SAD participants showed relatively (a) potentiated P1 amplitudes and fusiform gyrus (FG) activation to angry–neutral versus happy–neutral face pairs; (b) decreased P1 amplitudes to probes replacing emotional (angry and happy) versus neutral faces; and (c) higher sensitivity (d′) to probes following angry–neutral versus happy–neutral face pairs. SAD participants also showed significantly shorter reaction times (RTs) to probes replacing angry versus happy faces, but no group differences emerged for RT.

The results provide electrophysiological support for early hypervigilance to angry faces in SAD with involvement of the FG, and reduced visual processing of emotionally salient locations at later stages of information processing, which might be a manifestation of attentional avoidance.

Generalized social phobia (GSP) involves the fear/avoidance of social situations whereas generalized anxiety disorder (GAD) involves an intrusive worry about everyday life circumstances. It remains unclear whether these, highly co-morbid, conditions represent distinct disorders or alternative presentations of a single underlying pathology. In this study, we examined stimulus-reinforcement-based decision making in GSP and GAD.

Twenty unmedicated patients with GSP, 16 unmedicated patients with GAD and 19 age-, IQ- and gender-matched healthy comparison (HC) individuals completed the Differential Reward/Punishment Learning Task (DRPLT). In this task, the subject chooses between two objects associated with different levels of reward or punishment. Thus, response choice indexes not only reward/punishment sensitivity but also sensitivity to reward/punishment level according to between-object reinforcement distance.

We found that patients with GAD committed a significantly greater number of errors than both the patients with GSP and the HC individuals. By contrast, the patients with GSP and the HC individuals did not differ in performance on this task.

These results link GAD with anomalous non-affective-based decision making. They also indicate that GSP and GAD are associated with distinct pathophysiologies.

A number of western studies have suggested that the 6-month duration requirement of generalized anxiety disorder (GAD) does not represent a critical threshold in terms of onset, course, or risk factors of the disorder. No study has examined the consequences of modifying the duration requirement across a wide range of correlates in both developed and developing countries.

Population surveys were carried out in seven developing and 10 developed countries using the WHO Composite International Diagnostic Interview (total sample=85 052). Prevalence and correlates of GAD were compared across mutually exclusive GAD subgroups defined by different minimum duration criteria.

Lifetime prevalence estimates for GAD lasting 1 month, 3 months, 6 months and 12 months were 7.5%, 5.2%, 4.1% and 3.0% for developed countries and 2.7%, 1.8%, 1.5% and 1.2% for developing countries, respectively. There was little difference between GAD of 6 months' duration and GAD of shorter durations (1–2 months, 3–5 months) in age of onset, symptom severity or persistence, co-morbidity or impairment. GAD lasting ⩾12 months was the most severe, persistently symptomatic and impaired subgroup.

In both developed and developing countries, the clinical profile of GAD is similar regardless of duration. The DSM-IV 6-month duration criterion excludes a large number of individuals who present with shorter generalized anxiety episodes which may be recurrent, impairing and contributory to treatment-seeking. Future iterations of the DSM and ICD should consider modifying the 6-month duration criterion so as to better capture the diversity of clinically salient anxiety presentations.

Social anxiety often involves a combination of hypervigilance and avoidance to potentially warning signals including the facial expression of emotions. Functional imaging has demonstrated an increase in amygdala response to emotional faces in subjects with social anxiety. Nevertheless, it is unclear to what extent visual areas processing faces influence amygdala reactivity in different socially anxious individuals. We assessed the influence of the fusiform gyrus activation on amygdala response to emotional faces in the non-clinical range of social anxiety.

Twenty-two normal subjects showing a wide range in social anxiety scores were examined using functional magnetic resonance imaging (fMRI) during the processing of happy and fearful faces. A dimensional analysis approach was used involving voxel-wise mapping of the correlation between subjects' social anxiety scores and amygdala activation, before and after controlling for fusiform gyrus activation.

We observed that only after controlling for subjects' level of activation of the fusiform gyrus was there an association between social anxiety ratings and amygdala response to both happy and fearful faces. The fusiform gyrus influence was more robust during the fear condition. Of note, fusiform gyrus response to fearful faces showed a negative correlation with additional behavioral assessments related to avoidance, including social anxiety scores, harm avoidance and sensitivity to punishment.

Relevant interactions among the emotional face-processing stages exist in the non-clinical range of social anxiety that may ultimately attenuate amygdala responses. Future research will help to establish the role of this effect in a clinical context.

Functional brain abnormalities have been repeatedly demonstrated in schizophrenia but there is little data concerning their progression. For such studies to have credibility it is first important to establish the reproducibility of functional imaging techniques. The current study aimed to examine these factors in healthy controls and in unmedicated subjects at high genetic risk of the disorder: (i) to examine the reproducibility of task-related activation patterns, (ii) to determine if there were any progressive functional changes in high-risk subjects versus controls reflecting inheritance of the schizophrenic trait, and (iii) to examine changes over time in relation to fluctuating positive psychotic symptoms (i.e. state effects).

Subjects were scanned performing the Hayling sentence completion test on two occasions 18 months apart. Changes in activation were examined in controls and high-risk subjects (n=16, n=63). Reproducibility was assessed for controls and high-risk subjects who remained asymptomatic at both time points (n=16, n=32).

Intra-class correlation values indicated good agreement between scanning sessions. No significant differences over time were seen between the high-risk and control group; however, comparison of high-risk subjects who developed symptoms versus those who remained asymptomatic revealed activation increases in the left middle temporal gyrus (p=0.026).

The current results suggest that functional changes over time occur in the lateral temporal cortex as high genetic risk subjects become symptomatic, further, they indicate the usefulness of functional imaging tools for investigating progressive changes associated with state and trait effects in schizophrenia.

Depression is a frequent mood disorder that affects around 33% of stroke patients and has been associated with both poorer outcome and increased mortality. Our aim was to test the possible association between inflammatory and neurotrophic molecular markers and the development of post-stroke depression.

We studied 134 patients with a first episode of ischemic stroke without previous history of depression or speech disorders. We screened for the existence of major depression symptoms in accordance with DSM-IV criteria and a Yesavage Geriatric Depression Scale (GDS) score >11 at discharge and 1 month after stroke. At these times, serum levels of molecular markers of inflammation [interleukin (IL)−1β, IL-6, intracellular adhesion molecule 1 (ICAM-1), tumor necrosis factor (TNF)-α, leptin and high-sensitivity C-reactive protein (hs-CRP)] and neurotrophic factors [brain-derived neurotrophic factor (BDNF)] were measured by enzyme-linked immunosorbent assay (ELISA).

Twenty-five patients (18.7%) were diagnosed as having major depression at discharge. Out of 104 patients who completed the follow-up period, 23 were depressed at 1 month (22.1%). Patients with major depression showed higher serum leptin levels at discharge [43.4 (23.4–60.2) v. 6.4 (3.7–16.8) ng/ml, p<0.001] and at 1 month after stroke [46.2 (34.0–117.7) v. 6.4 (3.4–12.2) ng/ml, p<0.001). Serum levels of leptin >20.7 ng/ml were independently associated with post-stroke depression [odds ratio (OR) 16.4, 95% confidence interval (CI) 5.2–51.5, p<0.0001]. Leptin levels were even higher in the eight patients who developed depression after discharge [114.6 (87.6–120.2) v. 7.2 (3.6–13.6) ng/ml, p<0.0001].

Serum leptin levels at discharge are found to be associated with post-stroke depression and may predict its development during the next month.

Communication disturbance (thought disorder) is a central feature of schizophrenia that predicts poor functioning. We investigated the hypothesis that memory and attention deficits interact with beliefs about the gravity of being rejected (i.e. evaluation sensitivity) to produce the symptoms of communication disorder.

Seventy-four individuals diagnosed with schizophrenia or schizo-affective disorder completed a battery of tests assessing neurocognition (attention, working and verbal memory, abstraction), symptomatology (positive, negative and affective), functioning, and dysfunctional beliefs.

Patients with communication deviance (n=33) performed more poorly on the neurocognitive tests and reported a greater degree of sensitivity to rejection than patients with no thought disorder (n=41). In a logistic regression analysis, evaluation sensitivity moderated the relationship between cognitive impairment and the presence of communication disorder. This finding was independent of hallucinations, delusions, negative symptoms, depression and anxiety.

We propose that negative appraisals about acceptance instigate communication anomalies in individuals with a pre-existing diathesis for imperfect speech production.