Major depressive disorder (MDD) and anxiety disorders (ANX) are debilitating and prevalent conditions that often co-occur in adolescence and young adulthood. The leading theoretical models of their co-morbidity include the direct causation model and the shared etiology model. The present study compared these etiological models of MDD–ANX co-morbidity in a large, prospective, non-clinical sample of adolescents tracked through age 30.

Logistic regression was used to examine cross-sectional associations between ANX and MDD at Time 1 (T1). In prospective analyses, Cox proportional hazards models were used to examine T1 predictors of subsequent disorder onset, including risk factors specific to each disorder or common to both disorders. Prospective predictive effect of a lifetime history of one disorder (e.g. MDD) on the subsequent onset of the second disorder (e.g. ANX) was then examined. This step was repeated while controlling for common risk factors.

The findings supported relatively distinct profiles of risk between MDD and ANX depending on order of development. Whereas the shared etiology model best explained co-morbid cases in which MDD preceded ANX, direct causation was supported for co-morbid cases in which ANX preceded MDD.

Consistent with previous research, significant cross-sectional and prospective associations were found between MDD and ANX. The results of the present study suggest that different etiological models may characterize the co-morbidity between MDD and ANX based upon the temporal order of onset. Implications for classification and prevention efforts are discussed.

Designed as state measures to monitor treatment response, symptoms of anxiety and depression (SxAnxDep) also have trait-like characteristics. No comprehensive etiologic model for SxAnxDep has illuminated the inter-relationship between their state- and trait-like characteristics, while including key predictor variables.

In a prospective three-wave study of 2395 female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD), we examined, using structural equation modeling, how genes, childhood and past-year environmental stressors, personality and episodes of major depression (MD) and generalized anxiety disorder (GAD) influence SxAnxDep.

The best-fit model, which explained 68–74% of the variance in SxAnxDep, revealed two etiologic pathways. Stable levels of SxAnxDep resulted largely from neuroticism, which in turn was influenced by genetic and early environment risk factors. Occasion-specific influences resulted from stressful events mediated through episodes of MD or GAD. These two pathways, which had approximately equal influences on levels of SxAnxDep, were substantially correlated because the genetic, early environmental and personality factors that impacted on stable symptom levels also predisposed to event exposure and disorder onset. No significant interaction was seen between the two pathways.

SxAnxDep in women in the general population arise from two inter-related causal pathways. The first, the ‘trait-like’ pathway, reflects genetic and early environmental risk factors, and is mediated largely through personality. The second pathway is mediated through episodes of MD and GAD, and is the result of both recent environmental adversities and trait-like factors that influence event exposure and the probability of disorder onset.

There is relative little information about the prevalence and risk factors of co-morbid anxiety and depression in later life. These disorders are often associated with worse response to treatment than either condition alone, and researching their epidemiology in diverse settings is vital to policy makers. We therefore investigated the co-occurrence of anxiety and depressive syndromes amongst older adults living in developing countries and measured the separate and joint effect of these two disorders on levels of associated disability.

The 10/66 study carried out cross-cultural surveys of all residents aged 65 years or over (n=15021) in 11 sites in seven countries (People's Republic of China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru). Anxiety was measured by using the Geriatric Mental State Examination and the Automated Geriatric Examination for Computer Assisted Taxonomy diagnostic system. Depression was assessed according to International Classification of Diseases 10th revision (ICD-10) and EURO-D criteria. Disability was measured by using the World Health Organization's Disablement Assessment Scale Version II. Zero-inflated negative binomial regression models were used to investigate the association of common mental disorders and disability.

The prevalence of co-occurring anxiety and depression (with the exclusion of subthreshold disorders) ranged between 0.9% and 4.2% across sites. Gender, socio-economic status, urbanicity and physical co-morbidities were associated with the different co-morbid states. Having both disorders was linked to higher disability scores than having anxiety or depression alone.

Given the close association of co-morbid anxiety and depression with disability, new policies to improve prevention, recognition and treatment will be needed to adapt to ageing populations and their mental health needs.

Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety.

We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each.

Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life.

Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.

The different incidence rates of, and risk factors for, depression in different countries argue for the need to have a specific risk algorithm for each country or a supranational risk algorithm. We aimed to develop and validate a predictD-Spain risk algorithm (PSRA) for the onset of major depression and to compare the performance of the PSRA with the predictD-Europe risk algorithm (PERA) in Spanish primary care.

A prospective cohort study with evaluations at baseline, 6 and 12 months. We measured 39 known risk factors and used multi-level logistic regression and inverse probability weighting to build the PSRA. In Spain (4574), Chile (2133) and another five European countries (5184), 11 891 non-depressed adult primary care attendees formed our at-risk population. The main outcome was DSM-IV major depression (CIDI).

Six variables were patient characteristics or past events (sex, age, sex×age interaction, education, physical child abuse, and lifetime depression) and six were current status [Short Form 12 (SF-12) physical score, SF-12 mental score, dissatisfaction with unpaid work, number of serious problems in very close persons, dissatisfaction with living together at home, and taking medication for stress, anxiety or depression]. The C-index of the PSRA was 0.82 [95% confidence interval (CI) 0.79–0.84]. The Integrated Discrimination Improvement (IDI) was 0.0558 [standard error (s.e.)=0.0071, Zexp=7.88, p<0.0001] mainly due to the increase in sensitivity. Both the IDI and calibration plots showed that the PSRA functioned better than the PERA in Spain.

The PSRA included new variables and afforded an improved performance over the PERA for predicting the onset of major depression in Spain. However, the PERA is still the best option in other European countries.

Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect.

An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out.

The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002).

Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

Psychiatric disorders are common following traumatic brain injury (TBI). However, few studies have examined the course of disorder development and the influence of pre-injury psychiatric history. The present study aimed to examine the frequency of, and association between, psychiatric disorders occurring pre- and post-injury, and to examine the post-injury course of disorders.

Participants were 102 adults (75.5% male) with predominantly moderate-severe TBI. Participants were initially assessed for pre-injury and current disorders, and reassessed at 3, 6 and 12 months post-injury using the Structured Clinical Interview for DSM-IV Disorders (SCID).

Over half of the participants had a pre-injury psychiatric disorder; predominantly substance use, mood, and anxiety disorders. In the first year post-injury, 60.8% of participants had a psychiatric disorder, commonly anxiety and mood disorders. Post-injury disorders were associated with the presence of a pre-injury history (p<0.01), with 74.5% of participants with a pre-injury psychiatric history experiencing a post-injury disorder, which commonly presented at initial assessment or in the first 6 months. However, 45.8% of participants without a pre-injury history developed a novel post-injury disorder, which was less likely to emerge at the initial assessment and generally developed later in the year.

Despite evidence that most post-injury psychiatric disorders represent the continuation of pre-existing disorders, a significant number of participants developed novel psychiatric disorders. This study demonstrates that the timing of onset may differ according to pre-injury history. There seem to be different trajectories for anxiety and depressive disorders. This research has important implications for identifying the time individuals are most at risk of psychiatric disorders post-injury.

As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse.

A community sample of individuals aged 18–65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded.

A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median ‘go’ trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance.

Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.

Cannabis use is considered a component cause of psychotic illness, interacting with genetic and other environmental risk factors. Little is known, however, about these putative interactions. The present study investigated whether an urban environment plays a role in moderating the effects of adolescent cannabis use on psychosis risk.

Prospective data (n=1923, aged 14–24 years at baseline) from the longitudinal population-based German Early Developmental Stages of Psychopathology cohort study were analysed. Urbanicity was assessed at baseline and defined as living in the city of Munich (1562 persons per km2; 4061 individuals per square mile) or in the rural surroundings (213 persons per km2; 553 individuals per square mile). Cannabis use and psychotic symptoms were assessed three times over a 10-year follow-up period using the Munich version of the Composite International Diagnostic Interview.

Analyses revealed a significant interaction between cannabis and urbanicity [10.9% adjusted difference in risk, 95% confidence interval (CI) 3.2–18.6, p=0.005]. The effect of cannabis use on follow-up incident psychotic symptoms was much stronger in individuals who grew up in an urban environment (adjusted risk difference 6.8%, 95% CI 1.0–12.5, p=0.021) compared with individuals from rural surroundings (adjusted risk difference −4.1%, 95% CI −9.8 to 1.6, p=0.159). The statistical interaction was compatible with substantial underlying biological synergism.

Exposure to environmental influences associated with urban upbringing may increase vulnerability to the psychotomimetic effects of cannabis use later in life.

A cross-sectional study was conducted in participants with schizophrenia to explore a potential association between the patients' remission status and neurocognitive functioning and to examine whether these factors have an impact on functional outcome.

Psychopathological symptoms were rated by means of the Positive and Negative Syndrome Scale with symptom remission being assessed by applying the severity component of the recently proposed remission criteria. Tests for the cognitive battery were selected to cover domains known to be impaired in patients with schizophrenia. Next to pre-morbid intelligence, attention performance, executive functioning, verbal fluency, verbal learning and memory, working memory and visual memory were assessed. The joint effect of remission status and neurocognitive functioning on treatment outcome was investigated by logistic regression analysis.

Out of 140 patients included in the study, 62 were symptomatically remitted. Mean age, education and sex distribution were comparable in remitted and non-remitted patients. Remitted patients showed significantly higher values on tests of verbal fluency, alertness and optical vigilance. Both symptomatic remission as well as performance on tests of working memory and verbal memory had a significant effect on the patients' employment status.

In the present study neuropsychological measures of frontal lobe functioning were associated with symptomatic remission from schizophrenia. In addition, both symptomatic remission and performance on tests of working memory and verbal memory had a significant effect on the patients' employment status. Longitudinal follow-up data are needed to determine how the associations of these determinants of functional outcome interact and change over time.

Movement disorders and schizotypy are both prevalent in unaffected siblings of patients with schizophrenia and both are associated with the risk of developing psychosis or schizophrenia. However, to date there has been no research into the association between these two vulnerability factors in persons with an increased genetic risk profile. We hypothesized that unaffected siblings of patients with non-affective psychosis have more movement disorders and schizotypy than healthy controls and that these co-occur.

In a cross-sectional design we assessed the prevalence and inter-relationship of movement disorders and schizotypy in 115 unaffected siblings (mean age 27 years, 44% males) and 100 healthy controls (mean age 26 years, 51% males). Movement disorders were measured with the Abnormal Involuntary Movement Scale (AIMS), the Unified Parkinson Disease Rating Scale (UPDRS), the Barnes Akathisia Rating Scale (BARS), and one separate item for dystonia. Schizotypy was assessed with the Structured Interview for Schizotypy – Revised (SIS-R).

There were significant differences in the prevalence of movement disorders in unaffected siblings versus healthy controls (10% v. 1%, p<0.01) but not in the prevalence of schizotypy. Unaffected siblings with a movement disorder displayed significantly more positive and total schizotypy (p=0.02 and 0.03 respectively) than those without. In addition, dyskinesia correlated with positive schizotypy (r=0.51, p=0.02).

The association between movement disorders (dyskinesia in particular) with positive and total schizotypy in unaffected siblings suggests that certain vulnerability factors for psychosis or schizophrenia cluster in a subgroup of subjects with an increased genetic risk of developing the disease.

Current theories of post-traumatic stress disorder (PTSD) place considerable emphasis on the role cognitive distortions such as self-blame, hopelessness or preoccupation with danger play in the etiology and maintenance of the disorder. Previous studies have shown that cognitive distortions in the early aftermath of traumatic events can predict future PTSD severity but, to date, no studies have investigated the neural correlates of this association.

We conducted a prospective study with 106 acutely traumatized subjects, assessing symptom severity at three time points within the first 3 months post-trauma. A subsample of 20 subjects additionally underwent a functional 4-T magnetic resonance imaging (MRI) scan at 2 to 4 months post-trauma.

Cognitive distortions proved to be a significant predictor of concurrent symptom severity in addition to diagnostic status, but did not predict future symptom severity or diagnostic status over and above the initial symptom severity. Cognitive distortions were correlated with blood oxygen level-dependent (BOLD) signal strength in brain regions previously implicated in visual processing, imagery and autobiographic memory recall. Intrusion characteristics accounted for most of these correlations.

This investigation revealed significant predictive value of cognitive distortions concerning concurrent PTSD severity and also established a significant relationship between cognitive distortions and neural activations during trauma recall in an acutely traumatized sample. These data indicate a direct link between the extent of cognitive distortions and the intrusive nature of trauma memories.

Unlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial.

Seventy Iranian veterans of the Iran–Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50–200 mg/day) (n=35, completers=32) or placebo (n=35, completers=30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale – Revised (IES-R) and the Clinical Global Impression scale – Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ⩾30% reduction in the IES-R total score plus a CGI-I rating of ‘much’ or ‘very much’ improved.

On both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (p<0.001) and also in the CGI-S score (p<0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (p⩽0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% v. 3%, p⩽0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions.

The results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans.

Current rodent models emphasize the joint action of the stress mediators noradrenaline (NE) and cortisol (CORT) in conferring a memory advantage of emotional over neutral stimuli.

Using a pharmacological strategy of tackling this stress-related mechanism to enhance human episodic (autobiographical) memory, we measured amygdala-hippocampal responses during encoding of emotional and neutral stimuli with functional magnetic resonance imaging in 51 healthy subjects under four pharmacological conditions in a double-blind parallel group design: (i) placebo; (ii) the NE-reuptake inhibitor reboxetine (4 mg); (iii) hydrocortisone (synthetic CORT) (30 mg); or (iv) both agents in combination.

Differential drug effects were found in the left hippocampus, whereas hydrocortisone alone selectively decreased hippocampal responses to emotional relative to neutral stimuli, reboxetine potentiated hippocampal responses to these stimuli. Importantly, the inhibitory influence of hydrocortisone was reversed by co-administration of reboxetine.

Our results imply that stress levels of CORT alone attenuate hippocampal responses to emotional stimuli, an effect possibly related to a regulatory negative feedback loop. However, when simultaneously elevated to stress levels, NE and CORT act together to synergistically enhance hippocampal activity during encoding of emotional stimuli, a mechanism that may turn maladaptive under circumstances of traumatic stress.

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

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

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

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

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

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

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

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

The study aims to explore, using indirect ecological measures of exposure, the role of viral infections in the development of anorexia nervosa (AN).

The cohort of participants consisted of all female subjects born in the Veneto region in the period between 1970 and 1984, and residing in the urban and suburban area of Padua (27 682 female subjects in an area of 424 km2). The main outcome measure was the diagnosis of AN resulting from the Public Mental Health Database, the Register of Hospital Admissions, and the Register of the Eating Disorders Unit (n=402, 1.4%). The number of cases of rubella, chickenpox, influenza and measles was ascertained for each month for the 15-year period.

Exposures during the sixth month of pregnancy to the peaks of chickenpox [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2–2.0] and rubella infections (OR 1.5, 95% CI 1.1–2.0) were significantly associated with an increased risk of developing AN, even after controlling for socio-economic status, urbanization and month of birth. We found weak evidence of a season-of-birth bias.

In utero exposure to viral infection could be a risk factor for developing AN. We need further epidemiological and serological studies to confirm this hypothesis.

Psychiatric co-morbidity is complex and ubiquitous. Our aim was to describe the extent, nature and patterning of psychiatric co-morbidity within a representative sample of the adult population of England, using latent class analysis.

Data were used from the 2007 Adult Psychiatric Morbidity Survey, a two-phase national household survey undertaken in 2007 comprising 7325 participants aged 16 years and older living in private households in England. The presence of 15 common mental health and behavioural problems was ascertained using standardized clinical and validated self-report measures, including three anxiety disorders, depressive episode, mixed anxiety depressive disorder, psychosis, antisocial and borderline personality disorders, eating disorders, post-traumatic stress disorder, attention deficit disorder, alcohol and drug dependencies, problem gambling and attempted suicide.

A four-class model provided the most parsimonious and informative explanation of the data. Most participants (81.6%) were assigned to a non-symptomatic or ‘Unaffected’ class. The remainder were classified into three qualitatively different symptomatic classes: ‘Co-thymia’ (12.4%), ‘Highly Co-morbid’ (5.0%) and ‘Addictions’ (1.0%). Classes differed in mean numbers of conditions and impairments in social functioning, and these dimensions were correlated.

Our findings confirm that mental disorders typically co-occur and are concentrated in a relatively small number of individuals. Conditions associated with the highest levels of disability, mortality and cost – psychosis, suicidality and personality disorders – are often co-morbid with more common conditions. This needs to be recognized when planning services and when considering aetiology.

Longitudinal data from the 1970 British Cohort Study were used to examine the long-term adult outcomes of those who, as children, were placed in public care.

Multivariate logistic estimation models were used to determine whether public care and placement patterns were associated with adult psychosocial outcomes. Seven emotional and behavioural outcomes measured at age 30 years were considered: depression, life dissatisfaction, self-efficacy, alcohol problems, smoking, drug abuse, and criminal convictions.

The analyses revealed a significant association between public care status and adult maladjustment on depression [odds ratio (OR) 1.74], life dissatisfaction (OR 1.45), low self-efficacy (OR 1.95), smoking (OR 1.70) and criminal convictions (OR 2.13).

Overall, the present study findings suggest that there are enduring influences of a childhood admission to public care on emotional and behavioural adjustment from birth to adulthood. Some of the associations with childhood public care were relatively strong, particularly with respect to depression, self-efficacy and criminal convictions.