The working environment may have a significant effect on response to treatment of depression and this issue has not yet been sufficiently addressed in the scientific literature. There is evidence showing that being engaged in high-level positions can be an obstacle to the success of treatment. This article discusses the few evidence in the literature and some of the possible mechanisms involved. Specific personality attributes and difficulties in adapting to depression may delay access to care and may also reduce treatment compliance. The presence of stress in jobs that require high cognitive function and lack of social support may be elements that hinder the recovery process. Residual symptoms that impact on cognitive functions may undermine adherence to treatment and adversely affect the response. The implications of these issues are potentially relevant for clinical practice in the treatment of depression and for future research.

A previously unresearched Early Bronze Age dagger-grave found in 1989 at Racton, West Sussex, is profiled here through a range of studies. The dagger, the only grave accompaniment, is of the ‘transitional’ Ferry Fryston type, this example being of bronze rather than copper. Bayesian analysis of relevant radiocarbon dates is used to refine the chronology of the earliest bronze in Britain. While the Ferry Fryston type was current in the earlier half of the twenty-second century bc, the first butt-riveted bronze daggers did not emerge until the second half. The Racton dagger is also distinguished by its elaborate rivet-studded hilt, an insular innovation with few parallels.

The excavated skeleton was that of a senior male, buried according to the appropriate rites of the time. Isotopic profiling shows an animal-protein rich diet that is typical for the period, but also the likelihood that he was brought up in a region of older silicate sedimentary rocks well to the west or north west of Racton. He had suffered injury at or close to the time of death; a slice through the distal end of his left humerus would have been caused by a fine-edged blade, probably a dagger. Death as a result of combat-contested leadership is explored in the light of other injuries documented among Early Bronze Age burials. Codified elite-level combat could help to explain the apparent incongruity between the limited efficacy of early dagger forms and their evident weapon-status.

Two widely used diagnostic systems, the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are reviewed for their ability to define those who will benefit from active treatment rather than placebo. Both systems suffer from a weakness in defining symptoms sufficiently clearly to separate depression from normal mood variations in the general population. Consequently, normal individuals may be medicalized and defined as suffering from and treated for depression. Also, in mild depression, unlike moderate depression, a lack of significant separation of active treatment from placebo has been shown in individual double-blind, placebo-controlled studies and in meta-analyses of these treatment studies. Both systems would be more useful for treatment purposes if they provided a clearer symptomatic definition of moderate depression, as is widely used in pivotal regulatory standard efficacy studies.

The appearance of the distinctive ‘Beaker package’ marks an important horizon in British prehistory, but was it associated with immigrants to Britain or with indigenous converts? Analysis of the skeletal remains of 264 individuals from the British Chalcolithic–Early Bronze Age is revealing new information about the diet, migration and mobility of those buried with Beaker pottery and related material. Results indicate a considerable degree of mobility between childhood and death, but mostly within Britain rather than from Europe. Both migration and emulation appear to have had an important role in the adoption and spread of the Beaker package.

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.

What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of ~2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSR1 (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1–2 years is recommended before very gradual withdrawal may be considered.

All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.

What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healtcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been perform Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Obsessive-compulsive disorder (OCD) was thought to be a rather rare disorder and little attention was focused on investigations of the disorder until the first placebo-controlled studies reported efficacy. In 1980 three pivotal papers were published: Montgomery reported that clomipramine was effective in OCD without concomitant depression, and Thoren et al and Marks et al reported that clomipramine was effective in OCD with varying amounts of concomitant depression. These results opened the floodgates of psychopharmacological research and encouraged a more aggressive research program aimed at providing sufficient data for OCD to be recognized as a treatable condition.

What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in longterm treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

All the research to date implicates serotonin as the major neurotransmitter involved in obsessive-compulsive disorder (OCD). Much of the evidence has come from clinical treatment studies, which have shown the specific antiobsessional effect of drugs that are potent inhibitors of serotonin reuptake. Only the selective serotonin reuptake inhibitors (SSRIs) and the potent inhibitors of serotonin reuptake have been shown to be effective in treating patients with OCD. Serotonin receptor inhibitors and SSRIs have been thoroughly investigated in short- and long-term placebo-controlled studies and all have been found to be effective in OCD.

Background: Engaging clients from the outset of psychotherapy is important for therapeutic success. However, there is little research evaluating therapists’ initial attempts to engage clients in the therapeutic process. This article reports retrospective analysis of data from a trial of online cognitive behavioural therapy (CBT) for depression. Qualitative and quantitative methods were used to evaluate how therapists manage clients’ expectations at the outset of therapy and its relationship with client retention in the therapeutic intervention. Aims: To develop a system to codify expectation management in initial sessions of online CBT and evaluate its relationship with retention. Method: Initial qualitative research using conversation analysis identified three communication practices used by therapists at the start of first sessions: no expectation management, some expectation management, and comprehensive expectation management. These findings were developed into a coding scheme that enabled substantial inter-rater agreement (weighted Kappa = 0.78; 95% CI: 0.52 to 0.94) and was applied to all trial data. Results: Adjusting for a range of client variables, primary analysis of data from 147 clients found comprehensive expectation management was associated with clients remaining in therapy for 1.4 sessions longer than those who received no expectation management (95% CI: -0.2 to 3.0). This finding was supported by a sensitivity analysis including an additional 21 clients (1.6 sessions, 95% CI: 0.2 to 3.1). Conclusions: Using a combination of qualitative and quantitative methods, this study suggests a relationship between expectation management and client retention in online CBT for depression, which has implications for professional practice. A larger prospective study would enable a more precise estimate of retention.

Multiple reports have identified variation in the GABRA2 gene as contributing to the genetic susceptibility to alcohol dependence. However, both the mechanism behind this association, and the range of alcohol-related phenotypes affected by variation in this gene, are currently undefined. Other data suggest that the risk of alcohol dependence is increased by relative insensitivity to alcohol's intoxicating effects. We have therefore tested whether GABRA2 variation is associated with variation in the subjective and objective effects of a standard dose of alcohol in humans. Data on responses to alcohol from the Alcohol Challenge Twin Study (Martin et al., 1985) have been tested against allelic and haplotype information obtained by typing 41 single-nucleotide polymorphisms in or close to the GABRA2 gene. Nominally significant allelic associations (p < .05, without correction for multiple testing) were found for body sway, motor coordination, pursuit rotor and arithmetical computation tasks, and for the personality dimension of Neuroticism. Because of the large number of phenotypes tested, these possibly significant findings will need to be confirmed in further studies.

Human height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1521] polymorphisms). We genotyped large Caucasian samples from Australia (N = 3906) and the Netherlands (N = 1689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3cm) to the effect observed in the published adult meta-analysis. An effect of this size explains ~0.1% of the phenotypic variance in height — this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height.

A log-coffin excavated in the early nineteenth century proved to be well enough preserved in the early twenty-first century for the full armoury of modern scientific investigation to give its occupants and contents new identity, new origins and a new date. In many ways the interpretation is much the same as before: a local big man buried looking out to sea. Modern analytical techniques can create a person more real, more human and more securely anchored in history. This research team shows how.