Painful physical symptoms (PPS) are both common and reduce the likelihood of remission in major depressive disorder (MDD), based upon results of clinical trials in selected populations. Whether PPS significantly contribute to poorer treatment outcome overall in primary or specialty psychiatric care settings remains unclear.

Out-patients (n=2876) with MDD were treated in the first step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial with citalopram up to 60 mg/day for up to 14 weeks. Presence of painful symptoms, as well as severity of depression, physical illness, and demographic and treatment factors were examined. Time to and overall rates of remission were analysed in relation to the presence of PPS.

Of the participants, 80% complained of PPS. These patients, both in primary and specialty psychiatric settings, had significantly lower remission rates and took longer to remit. Increasing severity of PPS was associated with greater physical illness burden, lower socio-economic status, absence of private insurance and being female, African-American or Hispanic. After adjustment for these factors, patients with PPS no longer had significantly poorer treatment outcomes.

Presence and severity of PPS is an indicator of MDD that may have poorer treatment outcome with an initial selective serotonin reuptake inhibitor. These poorer treatment outcomes are multifactorial, however, and are not explained by the presence and severity of pain per se.

Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia.

fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age-matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object–location paired-associate memory task, with experimental manipulation of mnemonic load.

In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS.

Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis.

Dyadic discord, while common in depression, has not been specifically evaluated as an outcome predictor in chronic major depressive disorder. This study investigated pretreatment dyadic discord as a predictor of non-remission and its relationship to depressive symptom change during acute treatment for chronic depression.

Out-patients with chronic depression were randomized to 12 weeks of treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy or their combination. Measures included the Marital Adjustment Scale (MAS) and the Inventory of Depressive Symptomatology – Self Report (IDS-SR30). Of 681 original patients, 316 were partnered and 171 of these completed a baseline and exit MAS, and at least one post-baseline IDS-SR30. MAS scores were analysed as continuous and categorical variables (‘dyadic discord’ v. ‘no dyadic discord’ defined as an MAS score >2.36. Remission was defined as an IDS-SR30 of ⩽14 at exit (equivalent to a 17-item Hamilton Rating Scale for Depression of ⩽7).

Patients with dyadic discord at baseline had lower remission rates (34.1%) than those without dyadic discord (61.2%) (all three treatment groups) (χ2=12.6, df=1, p=0.0004). MAS scores improved significantly with each of the treatments, although the change was reduced by controlling for improvement in depression. Depression remission at exit was associated with less dyadic discord at exit than non-remission for all three groups [for total sample, 1.8 v. 2.4, t(169)=7.3, p<0.0001].

Dyadic discord in chronically depressed patients is predictive of a lower likelihood of remission of depression. Couple therapy for those with dyadic discord may increase remission rates.

Subjects at ‘ultra high risk’ (UHR) for developing psychosis have differences in white matter (WM) compared with healthy controls. WM integrity has not yet been investigated in UHR subjects in relation to the development of subsequent psychosis. Hence, we investigated a prospective cohort of UHR subjects comparing whole brain fractional anisotropy (FA) of those later developing psychosis (UHR-P) to those who did not (UHR-NP).

We recruited 37 subjects fulfilling UHR criteria and 10 healthy controls. Baseline 3 Tesla magnetic resonance imaging (MRI) scans and Positive and Negative Syndrome Scale (PANSS) ratings were obtained. UHR subjects were assessed at 9, 18 and 24 months for development of frank psychosis. We compared baseline FA of UHR-P to controls and UHR-NP subjects. Furthermore, we related clinical data to MRI outcome in the patient population.

Of the 37 UHR subjects, 10 had transition to psychosis. UHR-P subjects showed significantly lower FA values than control subjects in medial frontal lobes bilaterally. UHR-P subjects had lower FA values than UHR-NP subjects, lateral to the right putamen and in the left superior temporal lobe. UHR-P subjects showed higher FA values, compared with UHR-NP, in the left medial temporal lobe. In UHR-P, positive PANSS negatively correlated to FA in the left middle temporal lobe. In the total UHR group positive PANSS negatively correlated to FA in the right superior temporal lobe.

UHR subjects who later develop psychosis have differences in WM integrity, compared with UHR subjects who do not develop psychosis and to healthy controls, in brain areas associated with schizophrenia.

Visuospatial working memory (VSWM) deficits have not been investigated specifically in children with dysthymic disorder (DD), although they are associated with impairments in attention that commonly occur in DD. This study investigates VSWM impairment in children with DD.

A cross-sectional study of VSWM in 6- to 12-year-old children with medication-naive DD (n=26) compared to an age-, gender- and ‘performance IQ’ (PIQ)-matched healthy control group (n=28) was completed.

The DD group demonstrated impairment in VSWM, including impairment in the spatial span and strategy components of VSWM. Furthermore, the VSWM impairment remained after controlling for spatial span. Inattentive symptoms were significantly associated with the VSWM impairment.

This study of children with DD found deficits in performance on VSWM tasks, suggesting that fronto-striatal–parietal neural networks that underlie processes of attention and the executive component of VSWM are dysfunctional in children with DD. These findings further our understanding of DD and suggest more specific interventions that might improve functioning.

The same executive dysfunctions and alterations in neuroimaging tests (both functional and structural) have been found in obsessive-compulsive patients and their first-degree relatives. These neurobiological findings are considered to be intermediate markers of the disease. The aim of our study was to assess verbal and non-verbal memory in unaffected first-degree relatives, in order to determine whether these neuropsychological functions constitute a new cognitive marker for obsessive-compulsive disorder (OCD).

Recall and use of organizational strategies in verbal and non-verbal memory tasks were measured in 25 obsessive-compulsive patients, 25 unaffected first-degree relatives and 25 healthy volunteers.

First-degree relatives and healthy volunteers did not show differences on most measures of verbal memory. However, during the recall and processing of non-verbal information, deficits were found in first-degree relatives and patients compared with healthy volunteers.

The presence of the same deficits in the execution of non-verbal memory tasks in OCD patients and unaffected first-degree relatives suggests the influence of certain genetic and/or familial factors on this cognitive function in OCD and supports the hypothesis that deficits in non-verbal memory tasks could be considered as cognitive markers of the disorder.

Abnormalities in early social development and personality are present in patients with schizophrenia and their unaffected relatives. This study aimed to establish the degree to which these childhood and adolescent developmental abnormalities are genetically determined.

We used a combined twin and family study design (n=531) to assess childhood and adolescent social adjustment and schizotypal personality traits in 98 twin pairs (n=196) varying in their zygosity and concordance for schizophrenia and 156 sibling clusters (n=335) varying in their concordance for schizophrenia.

Schizophrenia was significantly associated with childhood and adolescent deficits in social adjustment and personality, with additive genetic effects being the main source of these phenotypic correlations.

Abnormalities of social adjustment and personality are present in children and adolescents who later develop schizophrenia, reflecting the influence of common genetic risk.

Deliberate self-harm (DSH) is a major public health problem, with young people most at risk. Lifetime prevalence of DSH in Irish adolescents is between 8% and 12%, and it is three times more prevalent among girls than boys. The aim of the study was to identify the psychological, life-style and life event factors associated with self-harm in Irish adolescents.

A cross-sectional study was conducted, with 3881 adolescents in 39 schools completing an anonymous questionnaire as part of the Child and Adolescent Self-harm in Europe (CASE) study. There was an equal gender balance and 53.1% of students were 16 years old. Information was obtained on history of self-harm life events, and demographic, psychological and life-style factors.

Based on multivariate analyses, important factors associated with DSH among both genders were drug use and knowing a friend who had engaged in self-harm. Among girls, poor self-esteem, forced sexual activity, self-harm of a family member, fights with parents and problems with friendships also remained in the final model. For boys, experiencing bullying, problems with schoolwork, impulsivity and anxiety remained.

Distinct profiles of boys and girls who engage in self-harm were identified. Associations between DSH and some life-style and life event factors suggest that mental health factors are not the sole indicators of risk of self-harm. The importance of school-related risk factors underlines the need to develop gender-specific initiatives in schools to reduce the prevalence of self-harm.

Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults.

In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors.

Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08).

Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

High Neuroticism and low Conscientiousness are frequently implicated in health-risk behaviors, such as smoking and overeating, as well as health outcomes, including mortality. Their associations with physiological markers of morbidity and mortality, such as inflammation, are less well documented. The present research examines the association between the five major dimensions of personality and interleukin-6 (IL-6), a pro-inflammatory cytokine often elevated in patients with chronic morbidity and frailty.

A population-based sample (n=4923) from four towns in Sardinia, Italy, had their levels of IL-6 measured and completed a comprehensive personality questionnaire, the NEO-PI-R. Analyses controlled for factors known to have an effect on IL-6: age; sex; smoking; weight; aspirin use; disease burden.

High Neuroticism and low Conscientiousness were both associated with higher levels of IL-6. The findings remained significant after controlling for the relevant covariates. Similar results were found for C-reactive protein, a related marker of chronic inflammation. Further, smoking and weight partially mediated the association between impulsivity-related traits and higher IL-6 levels. Finally, logistic regressions revealed that participants either in the top 10% of the distribution of Neuroticism or the bottom 10% of conscientiousness had an approximately 40% greater risk of exceeding clinically relevant thresholds of IL-6.

Consistent with the literature on personality and self-reported health, individuals high on Neuroticism or low on Conscientiousness show elevated levels of this inflammatory cytokine. Identifying critical medical biomarkers associated with personality may help to elucidate the physiological mechanisms responsible for the observed connections between personality traits and physical health.

Attitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available.

The Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated.

Evaluation of the ABC's internal consistency yielded Cronbach's α of 0.90–0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for all patients and for patients with each disorder. For patients with MDD, lower anticipated benefits of treatment was associated with less symptom improvement and lower odds of treatment response [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57–0.87, p=0.0011]. There was no association between ABC and symptom improvement or treatment response for patients with bipolar disorder or schizophrenia, possibly because these patients had modest benefits with treatment.

The ABC is the first self-report that measures patient expectations about the benefits of treatment on everyday functioning, filling an important gap in available assessments of attitudes and expectations about treatment. The ABC is simple, easy to use, and has acceptable psychometric properties for use in research or clinical settings.

Cognitive deficits in schizophrenia are well established and are known to be present during the first episode of a psychotic disorder. In addition, consistent heterogeneity within these impairments remains unexplained. One potential source of variability may be the level of pre-morbid adjustment prior to the onset of first-episode psychosis (FEP).

Ninety-four FEP patients and 32 healthy controls were assessed at baseline on several neuropsychological tests comprising six cognitive domains (verbal memory, visual memory, working memory, processing speed, reasoning/problem-solving and attention) and an abbreviated version of the full IQ. A global neurocognitive domain was also computed. Pre-morbid adjustment patterns were divided into three distinct groups: stable-poor, stable-good and deteriorating course.

Based on a cut-off of 0.8 for effect size, the stable-poor pre-morbid adjustment group was significantly more impaired on most cognitive domains and full IQ compared to the deteriorating group, who were more severely impaired on all measures compared to the stable-good group. The type of cognitive deficit within each subgroup did not differ and the results indicate that a global neurocognition measure may reliably reflect the severity of cognitive impairment within each subgroup.

Pre-morbid adjustment patterns prior to onset of psychosis are associated with severity but not type of cognitive impairment. Patients in the stable-poor group are generally more impaired compared to the deteriorating group, who are, in turn, more impaired than the stable-good group.

African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients.

We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls.

White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus.

We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.

Little research has focused on delineating the specific predictors of emotional over-involvement (EOI) and critical comments (CC) in the early course of psychosis. The purpose of this study was to investigate the differential relationships of EOI and CC with relevant predictors in relatives of first-episode psychosis (FEP) patients.

Baseline patient-related factors including psychotic symptoms, depression and duration of untreated psychosis (DUP) and carer attributes comprising CC, EOI, burden of care and carers' stress and depression were assessed in a cohort of 63 remitted FEP patients and their relatives. Carers were reassessed at 7 months follow-up.

Baseline analysis showed that EOI was more strongly correlated with family stress compared with CC, whereas CC yielded a stronger association with DUP than EOI. Carers' CC at follow-up was not significantly predicted by either baseline family stress, burden of care or patient-related variables. Conversely, baseline EOI predicted both family stress and burden of care at 7 months follow-up. Finally, family burden of care at follow-up was a function of baseline EOI and patients' depressive symptoms.

This study provides preliminary support to the postulate that EOI and CC may be influenced by separate factors early in the course of psychosis and warrant future research and therapeutic interventions as separate constructs. Implications for family interventions in the early phase of psychosis and the prevention of CC and EOI are discussed.

There is growing evidence on the importance of experiences of stressful events in the development of psychopathology. This study aimed to investigate the role of stressful events in the continuity of internalizing and externalizing problems, as well as the cross-influence of these problems from early childhood to late adolescence.

Data came from a general population sample of 396 children followed from the ages of 3 to 18 years. Parent-ratings of internalizing and externalizing problems at ages 3, 5, 10 and 18 years were used. Parents also reported on the presence of stressful events between the ages of 3 and 5 years, and 5 and 10 years. Adolescent reports on stressful events over the ages of 10–18 years were used. Structural equation models were used to disentangle/analyse the role of stressful events in the development of internalizing and externalizing problems.

From the age of 3 years onwards externalizing symptoms predicted experiences of stressful events. In turn, these experiences predicted later externalizing problems. Stressful events also explained part of the continuity of internalizing problems from the age of 10 years onwards, but not during childhood. From childhood onwards, cross-influences from externalizing problems to subsequent internalizing problems were found to run through stressful events. Only in adolescence cross-influences from internalizing problems to externalizing problems were found, again via stressful events.

From childhood onwards to late adolescence, stressful events play a significant role in both the continuity and the co-occurrence of externalizing and internalizing problems. Theoretical and methodological implications of these findings are discussed.

Previous imaging studies have revealed that acute major depression is characterized by altered neural responses to negative emotional stimuli. Typically, responses in limbic regions such as the amygdala are increased while activity in cortical regulatory regions such as the dorsolateral prefrontal cortex (DLPFC) is diminished. Whether these changes persist in unmedicated recovered patients is unclear.

We used functional magnetic resonance imaging to examine neural responses to emotional faces in a facial expression-matching task in 16 unmedicated recovered depressed patients and 21 healthy controls.

Compared with controls, recovered depressed patients had increased responses bilaterally to fearful faces in the DLPFC and right caudate. Responses in the amygdala did not distinguish the groups.

Our findings indicate that clinical recovery from depression is associated with increased activity in the DLPFC to negative emotional stimuli. We suggest that this increase may reflect a compensatory cortical control mechanism with the effect of limiting emotional dysregulation in limbic regions such as the amygdala.

Cognitive-behavioral therapy (CBT) consisting of exposure and response prevention (EX/RP) is efficacious as a treatment for obsessive–compulsive disorder (OCD). However, about half of patients have a partial or poor response to EX/RP treatment. This study examined potential predictors and moderators of CBT augmentation of pharmacotherapy, to identify variables associated with a poorer response to OCD treatment.

Data were drawn from a large randomized controlled trial that compared the augmenting effects of EX/RP to stress management training (SMT; an active CBT control) among 108 participants receiving a therapeutic dose of a serotonin reuptake inhibitor (SRI). Stepwise regression was used to determine the model specification.

Pretreatment OCD severity and gender were significant moderators of outcome: severity affected SMT (but not EX/RP) outcome; and gender affected EX/RP (but not SMT) outcome. Adjusting for treatment type and pretreatment severity, significant predictors included greater co-morbidity, number of past SRI trials, and lower quality of life (QoL). Significant moderators, including their main-effects, and predictors accounted for 37.2% of the total variance in outcome, comparable to the impact of treatment type alone (R2=30.5%). These findings were replicated in the subgroup analysis of EX/RP alone (R2=55.2%).

This is the first randomized controlled study to examine moderators and predictors of CBT augmentation of SRI pharmacotherapy. Although effect sizes for individual predictors tended to be small, their combined effect was comparable to that of treatment. Thus, future research should examine whether monitoring for a combination of these risk factors and targeting them with multi-modular strategies can improve EX/RP outcome.

Symptoms of post-traumatic stress disorder (PTSD) and depression are highly co-morbid following a traumatic event. Nevertheless, decisive evidence regarding the direction of the relationship between these clinical entities is missing.

The aim of the present study was to examine the nature of this relationship by comparing a synchronous change model (PTSD and depression are time synchronous, possibly stemming from a third common factor) with a demoralization model (i.e. PTSD symptoms causing depression) and a depressogenic model (i.e. depressive symptoms causing PTSD symptoms). Israeli adult victims of single-event traumas (n=156) were assessed on measures of PTSD and depression at 2, 4 and 12 weeks post-event.

A cross-lagged structural equation modeling (SEM) analysis provided results consistent with the synchronous change model and the depressogenic model.

Depressive symptoms may play an important role in the development of post-traumatic symptoms.

Empirical evidence of the efficacy and effectiveness of psychosocial family intervention and of the specificity of its effects on the course of schizophrenia is limited. The aim was to study the efficacy and effectiveness of psychosocial family intervention with regard to clinical and social functioning and family burden after controlling for compliance and several prognostic factors.

A 2-year randomized controlled trial with blind assessments. Fifty patients with DSM-IV schizophrenia and persistent positive symptoms and/or previous clinical relapse were allocated to psychosocial family intervention, individual counselling and standard treatment versus individual counselling and standard treatment.

Family intervention was associated with fewer clinical relapses, hospitalizations and major incidents, and an improvement in positive and negative symptoms, social role performance, social relations, employment and family burden. The reduction in hospitalizations in the family intervention group was significantly greater than that observed in the group of patients who refused to participate but this was not the case for the control group. The effects of family intervention were independent of compliance and prognostic factors.

Family intervention is effective in severe schizophrenia independently of compliance and prognostic factors.

There is some evidence that cognitive therapy (CT) is beneficial in reducing relapses in bipolar disorder. However, not all bipolar patients benefit from it. A previous study found that a group of non-responders to CT shared common characteristics: they value some of the high goal-attainment beliefs and characteristics associated with being in a state of mild hypomania – a high ‘sense of hyper-positive self’ (SHPS). To promote of our understanding of this group of patients, the present study investigated the relationship between SHPS, preferred internal state, dysfunctional attitudes and coping with hypothetical manic prodromal scenarios.

Fifty-four bipolar I patients filled in self-report questionnaires that assess preferred mood state, coping with scenarios, dysfunctional attitudes and SHPS.

The Sense of Hyper-positive Self Scale Ideal score (SHPSS-Ideal) predicted patients' preferred internal state of mania. Coping with hypothetical scenarios was predicted by Dysfunctional Attitude Scale (DAS) goal-attainment scores: the higher the goal-attainment score, the higher the participant's tendency to identify with self-descriptors linked to hypomania and to engage in stimulating behaviours that may escalate the prodromal stage to mania.

Clinicians should check and modify goal-attainment beliefs, particularly of those who exhibit features of SHPS. These patients' tendency to identify with hypomanic traits as self-descriptors should be dealt with by psychological techniques such as cognitive restructuring.