Attentional Control as a Predictor of Response to Psychological Treatment for Depression and Relapse up to 1 year After Treatment: A Pilot Cohort Study.

BACKGROUND: Identifying depressed patients unlikely to reach remission and those likely to relapse after reaching remission is of great importance, but there are few pre-treatment factors that can help clinicians predict prognosis and together these explain relatively little variance in treatment outcomes. Attentional control has shown promise in studies to date, but has not been investigated prospectively in routine clinical settings with depressed patients. AIMS: This study aimed to pilot the use of a brief self-report measure of attentional control in routine care and investigate the associations between attentional control, psychological treatment response and relapse to depression up to 1 year post-treatment. METHOD: Depressed patients were recruited from two primary care psychological treatment (IAPT) services and completed the Attentional Control Scale (ACS) alongside routine symptom measures at every therapy session. Participants were tracked and followed up for 1 year post-treatment. RESULTS: Baseline ACS scores were associated with remission and residual depressive symptoms post-treatment, and relapse within 12 months of ending treatment, all independent of pre-treatment depressive symptom severity, and the latter also independent of residual symptoms. CONCLUSION: A self-report measure of attentional control can potentially be used to predict levels of depressive symptoms post-treatment and can contribute to predicting risk of relapse to depression in IAPT services, without affecting rates of therapy completion/drop-out or data completion of standard IAPT measures. However, this pilot study had a small overall sample size and a very small number of observed relapses, so replication in a larger study is needed before firm conclusions can be made.

Assessing preschoolers interactive behaviour: A validation study of the "Coding System for Mother-Child Interaction".

BACKGROUND: The preschool years are a period of great developmental achievements, which impact critically on a child's interactive skills. Having valid and reliable measures to assess interactive behaviour at this stage is therefore crucial. The aim of this study was to describe the adaptation and validation of the child coding of the Coding System for Mother-Child Interactions and discuss its applications and implications in future research and practice. METHODS: Two hundred twenty Portuguese preschoolers and their mothers were videotaped during a structured task. Child and mother interactive behaviours were coded based on the task. Maternal reports on the child's temperament and emotional and behaviour problems were also collected, along with family psychosocial information. RESULTS: Interrater agreement was confirmed. The use of child Cooperation, Enthusiasm, and Negativity as subscales was supported by their correlations across tasks. Moreover, these subscales were correlated with each other, which supports the use of a global child interactive behaviour score. Convergent validity with a measure of emotional and behavioural problems (Child Behaviour Checklist 1 ½-5) was established, as well as divergent validity with a measure of temperament (Children's Behaviour Questionnaire-Short Form). Regarding associations with family variables, child interactive behaviour was only associated with maternal behaviour. CONCLUSIONS: Findings suggest that this coding system is a valid and reliable measure for assessing child interactive behaviour in preschool age children. It therefore represents an important alternative to this area of research and practice, with reduced costs and with more flexible training requirements. Attention should be given in future research to expanding this work to clinical populations and different age groups.

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors.

BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors. METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance. RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset. CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Low incidence of psychosis in Italy: confirmation from the first epidemiological study in Sicily.

PURPOSE: The incidence of psychotic disorders varies in different geographical areas. As there have been no reports from Southern Italy, this study aimed to determine the incidence rate of first-episode psychosis in Palermo, Sicily. METHODS: All patients, aged 18-65 years, presenting with a first episode of psychosis (FEP) (ICD-10 F20-29, F30-33) to mental health services in Palermo, were recorded over a 3-year period. Incidence rates of psychotic disorders and their 95% confidence intervals (95% CI) were estimated. Poisson regression was applied to estimate the differences in incidence rate ratio (IRR) by age, sex and migrant status. RESULTS: Two hundred and four FEP participants were identified during the 3 years; 183 (89.7%, males n = 112) participants were native Italians and 21 were migrants (10.3%, males n = 14). The crude incidence of all psychoses was 15.9 (95% CI 13.7-18.1). As predicted, the risk of schizophrenia F20 was higher in males compared to females (adjusted IRR = 1.99, 95% CI 1.36-2.88) and in migrants compared to native Italians (adjusted IRR = 4.02, 95% CI 2.39-6.75). CONCLUSIONS: This study, the first from Sicily, confirms previous findings from Northern Italy that the risk of schizophrenia and other psychoses is much lower in Italian cities than those reported from cities in Northern Europe; the reasons for this disparity may provide important clues to the aetiology of psychosis.

Biological and psychosocial risk factors for psychotic major depression.

AIMS: Few studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders. METHODS: Based on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs. RESULTS: Living alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD. CONCLUSIONS: Risk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.

Diagnostic change 10 years after a first episode of psychosis.

BACKGROUND: A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change. METHOD: Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests. RESULTS: Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis. CONCLUSIONS: Diagnoses other than schizophrenia should to be regarded as potentially provisional.

Reappraising the long-term course and outcome of psychotic disorders: the AESOP-10 study.

BACKGROUND: Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare. METHOD: AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews. RESULTS: At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1-4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London. CONCLUSIONS: Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.

Modelling the interplay between childhood and adult adversity in pathways to psychosis: initial evidence from the AESOP study.

BACKGROUND: There is evidence that a range of socio-environmental exposures is associated with an increased risk of psychosis. However, despite the fact that such factors probably combine in complex ways to increase risk, the majority of studies have tended to consider each exposure separately. In light of this, we sought to extend previous analyses of data from the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study on childhood and adult markers of disadvantage to examine how they combine to increase risk of psychosis, testing both mediation (path) models and synergistic effects. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK (n = 390) and a series of community controls (n = 391) were included in the AESOP study. Data relating to clinical and social variables, including parental separation and loss, education and adult disadvantage, were collected from cases and controls. RESULTS: There was evidence that the effect of separation from, but not death of, a parent in childhood on risk of psychosis was partially mediated through subsequent poor educational attainment (no qualifications), adult social disadvantage and, to a lesser degree, low self-esteem. In addition, there was strong evidence that separation from, but not death of, a parent combined synergistically with subsequent disadvantage to increase risk. These effects held for all ethnic groups in the sample. CONCLUSIONS: Exposure to childhood and adult disadvantage may combine in complex ways to push some individuals along a predominantly sociodevelopmental pathway to psychosis.

Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes.

BACKGROUND: Hippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis. METHOD: Magnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor. RESULTS: BHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI. CONCLUSIONS: BHI occurs in a minority of patients following their first psychotic episode and is associated with good outcome across clinical, functional and cognitive domains.

Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study.

BACKGROUND: To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. METHOD: One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. RESULTS: At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). CONCLUSIONS: We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data.

Post-traumatic stress symptoms in childhood brain tumour survivors and their parents.

OBJECTIVES: This study aimed to investigate post-traumatic stress symptoms (PTSS) in childhood brain tumour survivors and their parents. A further aim was to explore the relationship between objective illness parameters, parent-child interactions, coping styles and PTSS. METHODS: A cross-sectional correlational design was employed. Fifty-two childhood brain tumour survivors, aged 8-16, and 52 parents completed a battery of questionnaires designed to assess quality of parent-child interactions, monitoring and blunting attentional coping styles and PTSS. RESULTS: Over one-third (35%) of survivors and 29% of their parents reported severe levels of PTSS (suggestive of post-traumatic stress disorder 'caseness'). Increased parent-child conflict resolution for survivors and number of tumour recurrences for parents independently predicted the variance in PTSS. CONCLUSIONS: For a substantial proportion of brain tumour survivors and their parents the process of survivorship is a considerably distressing experience.

Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder.

BACKGROUND: Childhood adversity has been associated with onset of psychosis in adulthood but these studies have used only general definitions of this environmental risk indicator. Therefore, we sought to explore the prevalence of more specific adverse childhood experiences amongst those with and without psychotic disorders using detailed assessments in a large epidemiological case-control sample (AESOP). METHOD: Data were collected on 182 first-presentation psychosis cases and 246 geographically matched controls in two UK centres. Information relating to the timing and frequency of exposure to different types of childhood adversity (neglect, antipathy, physical and sexual abuse, local authority care, disrupted living arrangements and lack of supportive figure) was obtained using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Psychosis cases were three times more likely to report severe physical abuse from the mother that commenced prior to 12 years of age, even after adjustment for other significant forms of adversity and demographic confounders. A non-significant trend was also evident for greater prevalence of reported severe maternal antipathy amongst those with psychosis. Associations with maternal neglect and childhood sexual abuse disappeared after adjusting for maternal physical abuse and antipathy. Paternal maltreatment and other forms of adversity were not associated with psychosis nor was there evidence of a dose-response effect. CONCLUSIONS: These findings suggest that only specific adverse childhood experiences are associated with psychotic disorders and only in a minority of cases. If replicated, this greater precision will ensure that research into the mechanisms underlying the pathway from childhood adversity to psychosis is more fruitful.

Illicit substance use and its correlates in first episode psychosis.

OBJECTIVE: To determine if substance use (particularly cannabis) is more frequent among first episode psychosis patients and associated with a more problematic clinical presentation. METHOD: All first episode psychosis (FEP) patients presenting to secondary services were recruited from London and Nottingham, over 2 years, in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study broad framework. Clinical and sociodemographic variables were assessed using a set of standardized instruments. A schedule was created to retrospectively collate substance use data from patients, relatives and clinicians. RESULTS: Five hundred and eleven FEP were identified. They used three to five times more substances than general population. Substance use was associated with poorer social adjustment and a more acute mode of onset. Cannabis use did not affect social adjustment, but was associated with a more acute mode of onset. CONCLUSION: Cannabis has a different impact on FEP than other substances. Large epidemiological studies are needed to disentangle cannabis effect.

The biological underpinnings of perinatal depressive symptoms: A multi-systems approach.

BACKGROUND: Well-established evidence exists of an association between depressive symptoms and alterations in the stress and inflammatory response systems; however, the picture is far less coherent during the perinatal period. This study combines the assessment of multiple stress and inflammatory biomarkers in late pregnancy and after delivery in order to investigate cross-sectional and prospective associations with perinatal depressive symptoms. METHODS: One-hundred-ten healthy women were assessed in late pregnancy (mean gestational age=34.76; SD=1.12) and 89 were re-evaluated after delivery (mean hours after delivery=52.36; SD=19.70) for depressive and anxiety symptoms through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. Serum Interleukin-6 (IL-6), C-Reactive Protein (CRP) and diurnal salivary cortisol levels were measured on both occasions, while diurnal salivary alpha amylase (sAA) levels were assessed in late pregnancy. RESULTS: Using Hierarchical Linear Models, higher depressive symptoms were found to be associated with higher IL-6 levels, lower morning cortisol levels and a flatter cortisol diurnal slope during pregnancy, while adjusting for potential confounders. No significant associations were found after delivery or with change in biomarker levels from pre- to post-partum. Furthermore, preliminary evidence of a positive association between inflammation and stress markers in women with higher antenatal depressive symptoms was found. LIMITATIONS: The sample was relatively small and highly selected, thus limiting generalizability of the findings. CONCLUSIONS: Results emphasize the need for an integrated multi-systems approach to the understanding of the biological underpinnings of perinatal depression and suggest that the stress-immune interactions represent a promising avenue for future endeavor.

Combining dimensional and categorical representation of psychosis: the way forward for DSM-V and ICD-11?

BACKGROUND: There is good evidence that psychotic symptoms segregate into symptom dimensions. However, it is still unclear how these dimensions are associated with risk indicators and other clinical variables, and whether they have advantages over categorical diagnosis in clinical practice. We investigated symptom dimensions in a first-onset psychosis sample and examined their associations with risk indicators and clinical variables. We then examined the relationship of categorical diagnoses to the same variables. METHOD: We recruited 536 patients as part of a population-based, incidence study of psychosis. Psychopathology was assessed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). A principal axis factor analysis was performed on symptom scores. The relationship of dimension scores with risk indicators and with clinical variables was then examined employing regression analyses. Finally, regression models were compared to assess the contribution of dimensions versus diagnosis in explaining these variables. RESULTS: Factor analysis gave rise to a five-factor solution of manic, reality distortion, negative, depressive and disorganization symptom dimensions. The scores of identified dimensions were differentially associated with specific variables. The manic dimension had the highest number of significant associations; strong correlations were observed with shorter duration of untreated psychosis, acute mode of onset and compulsory admission. Adding dimensional scores to diagnostic categories significantly increased the amount of variability explained in predicting these variables; the reverse was also true but to a lesser extent. CONCLUSIONS: Categorical and dimensional representations of psychosis are complementary. Using both appears to be a promising strategy in conceptualising psychotic illnesses.

Ethnicity, social disadvantage and psychotic-like experiences in a healthy population based sample.

OBJECTIVE: We sought to investigate the prevalence and social correlates of psychotic-like experiences in a general population sample of Black and White British subjects. METHOD: Data were collected from randomly selected community control subjects, recruited as part of the AESOP study, a three-centre population based study of first-episode psychosis. RESULTS: The proportion of subjects reporting one or more psychotic-like experience was 19% (n = 72/372). These were more common in Black Caribbean (OR 2.08) and Black African subjects (OR 4.59), compared with White British. In addition, a number of indicators of childhood and adult disadvantage were associated with psychotic-like experiences. When these variables were simultaneously entered into a regression model, Black African ethnicity, concentrated adult disadvantage, and separation from parents retained a significant effect. CONCLUSION: The higher prevalence of psychotic-like experiences in the Black Caribbean, but not Black African, group was explained by high levels of social disadvantage over the life course.

Beyond the HPA-axis: Exploring maternal prenatal influences on birth outcomes and stress reactivity.

Accumulating evidence suggests that antenatal maternal stress is associated with altered behavioral and physiological outcomes in the offspring, however, whether this association is causal and the underlying biological mechanisms remain largely unknown. While the most studied mediator of maternal stress influences on the fetus has generally been cortisol, alternative novel markers of stress or inflammation warrant further consideration. The current investigation explored the influence of variations in self-reported symptoms of distress, stress hormones and inflammatory markers on infant birth outcomes and early stress regulation. The sample consisted of 104 pregnant women (mean gestational age = 34.76; SD = 1.12) and their healthy newborns. Maternal self-reported symptoms of depression and anxiety were evaluated through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory and levels of serum Interleukine-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) were measured in late pregnancy. Newborns' cortisol and behavioral response to the heel-stick was assessed 48-72 hours after birth. The associations between maternal stress measures and infant birth outcomes and stress reactivity, adjusted for potential confounders, were examined through hierarchical linear regressions and hierarchical linear models. Higher maternal IL-6 levels were associated with smaller head circumference at birth, while diurnal sAA levels were positively associated with birthweight. Maternal diurnal cortisol was related to newborn's stress reactivity: a flatter infant cortisol response to the heel-stick was associated with greater maternal cortisol increases after awakening during pregnancy, while greater infant behavioural reactivity was related to a flatter maternal diurnal cortisol profile. The observational nature of these data does not allow for causal inferences but the current findings illustrate that antenatal factors related to alterations in maternal stress and immune response systems are associated with fetal growth and neonatal stress reactivity. This may have implications for later health and psychological outcomes.

Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis.

PURPOSE: To review and synthesise prognostic indices that predict subsequent risk, prescriptive indices that moderate treatment response, and mechanisms that underlie each with respect to relapse and recurrence of depression in adults. RESULTS AND CONCLUSIONS: Childhood maltreatment, post-treatment residual symptoms, and a history of recurrence emerged as strong prognostic indicators of risk and each could be used prescriptively to indicate who benefits most from continued or prophylactic treatment. Targeting prognostic indices or their "down-stream" consequences will be particularly beneficial because each is either a cause or a consequence of the causal mechanisms underlying risk of recurrence. The cognitive and neural mechanisms that underlie the prognostic indices are likely addressed by the effects of treatments that are moderated by the prescriptive factors. For example, psychosocial interventions that target the consequences of childhood maltreatment, extending pharmacotherapy or adapting psychological therapies to deal with residual symptoms, or using cognitive or mindfulness-based therapies for those with prior histories of recurrence. Future research that focuses on understanding causal pathways that link childhood maltreatment, or cognitive diatheses, to dysfunction in the neocortical and limbic pathways that process affective information and facilitate cognitive control, might result in more enduring effects of treatments for depression.