Home alone: Social functioning as a transdiagnostic marker of mental health in youth, exploring retrospective and daily life measurements.

PURPOSE: Early detection and intervention of mental health problems in youth are topical given that mental disorders often start early in life. Young people with emerging mental disorders however, often present with non-specific, fluctuating symptoms. Recent reports indicate a decline in social functioning (SF) as an early sign of specific emerging mental disorders such as depression or anxiety, making SF a favorable transdiagnostic approach for earlier detection and intervention. Our aim was to investigate the value of SF in relation to transdiagnostic symptoms, and as a predictor of psychopathology over time, while exploring traditional retrospective versus innovative daily diary measurements of SF in youth. METHOD: Participants (N = 75) were 16-25 years of age and presented early stage psychiatric symptomatology. Psychiatric symptoms, including anxiety and depression, as well as SF -both in retrospect and in daily life- were assessed at two time points and analyzed cross-sectionally and longitudinally. RESULTS: A significant and negative association between SF and all psychiatric symptoms was found, and SF was a significant predictor of change in general psychiatric symptoms over time. Results were only significant when SF was measured traditionally retrospective. CONCLUSION: This study confirms a distinct relation between SF and transdiagnostic psychiatric symptoms in youth, even in a (sub)clinical population, and points towards SF as a predictor of transdiagnostic psychiatric symptoms. Further research is needed to learn more about the added value of daily life versus retrospective measurements.

From laboratory to life: associating brain reward processing with real-life motivated behaviour and symptoms of depression in non-help-seeking young adults.

BACKGROUND: Depression has been associated with abnormalities in neural underpinnings of Reward Learning (RL). However, inconsistencies have emerged, possibly owing to medication effects. Additionally, it remains unclear how neural RL signals relate to real-life behaviour. The current study, therefore, examined neural RL signals in young, mildly to moderately depressed - but non-help-seeking and unmedicated - individuals and how these signals are associated with depressive symptoms and real-life motivated behaviour. METHODS: Individuals with symptoms along the depression continuum (n = 87) were recruited from the community. They performed an RL task during functional Magnetic Resonance Imaging and were assessed with the Experience Sampling Method (ESM), completing short questionnaires on emotions and behaviours up to 10 times/day for 15 days. Q-learning model-derived Reward Prediction Errors (RPEs) were examined in striatal areas, and subsequently associated with depressive symptoms and an ESM measure capturing (non-linearly) how anticipation of reward experience corresponds to actual reward experience later on. RESULTS: Significant RPE signals were found in the striatum, insula, amygdala, hippocampus, frontal and occipital cortices. Region-of-interest analyses revealed a significant association between RPE signals and (a) self-reported depressive symptoms in the right nucleus accumbens (b = -0.017, p = 0.006) and putamen (b = -0.013, p = .012); and (b) the quadratic ESM variable in the left (b = 0.010, p = .010) and right (b = 0.026, p = 0.011) nucleus accumbens and right putamen (b = 0.047, p < 0.001). CONCLUSIONS: Striatal RPE signals are disrupted along the depression continuum. Moreover, they are associated with reward-related behaviour in real-life, suggesting that real-life coupling of reward anticipation and engagement in rewarding activities might be a relevant target of psychological therapies for depression.

High Incidence and Prevalence of Drug-Related Movement Disorders in Young Patients With Psychotic Disorders.

BACKGROUND: Drug-related movement disorders (DRMDs) reduce quality of life and contribute to medication noncompliance of patients with psychotic disorders. Little is known about the epidemiology of DRMDs in relatively young patients a few years after onset of psychosis. This is an important period to study, as the impact of the antipsychotic treatment on the long-term potentiation of the neural pathways associated with psychotic disorders and DRMDs is still minimal. This study investigated the prevalence, incidence, persistence, and clinical correlates of DRMDs in patients during their first years after disease onset. METHODS: The Genetic Risk and Outcome of Psychosis study is a longitudinal study of 1120 relatively young patients with nonaffective psychosis and a mean age and illness duration of 27 and 4 years, respectively. The following drug-related movement disorders were assessed at baseline and at the 3-year follow-up: parkinsonism, akathisia, tardive dyskinesia, and tardive dystonia. We determined prevalence, incidence, and persistence and investigated clinical correlates at and over the baseline and follow-up assessment. RESULTS: Patients' mean age and illness duration at baseline were 27.1 and 4.3 years, respectively. In 4 patients, 1 developed a DRMD over the 3-year study period. Prevalence, incidence, and persistence rates were highest for parkinsonism (32%, 21%, and 53%) followed by akathisia (9%, 5%, and 17%) and tardive dyskinesia (4%, 3%, and 20%). Significant associations were found between DRMDs and the patients' age, IQ, and psychopathology. CONCLUSIONS: The prevalence, persistence, and incidence of DRMDs in this sample were high despite the relatively young age, recent onset of the disorder, and treatment primarily with second-generation antipsychotics. These findings emphasize that screening, diagnosis, and treatment of DRMDs are still important.

Bright light therapy in pregnant women with major depressive disorder: study protocol for a randomized, double-blind, controlled clinical trial.

BACKGROUND: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. METHODS: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. DISCUSSION: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. TRIAL REGISTRATION: Netherlands Trial Register NTR5476 . Registered 5 November 2015.

Psychotic disorder and educational achievement: a family-based analysis.

BACKGROUND: Early social and cognitive alterations in psychotic disorder, associated with familial liability and environmental exposures, may contribute to lower than expected educational achievement. The aims of the present study were to investigate (1) how differences in educational level between parents and their children vary across patients, their healthy siblings, and healthy controls (effect familial liability), and across two environmental risk factors for psychotic disorder: childhood trauma and childhood urban exposure (effect environment) and (2) to what degree the association between familial liability and educational differential was moderated by the environmental exposures. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 629), 552 non-psychotic siblings and 326 healthy controls from the Netherlands and Belgium were studied. Participants reported their highest level of education and that of their parents. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire-Short Form. Urban exposure, expressed as population density, was rated across five levels. RESULTS: Overall, participants had a higher level of education than their parents. This difference was significantly reduced in the patient group, and the healthy siblings displayed intergenerational differences that were in between those of controls and patients. Higher levels of childhood urban exposure were also associated with a smaller intergenerational educational differential. There was no evidence for differential sensitivity to childhood trauma and childhood urbanicity across the three groups. CONCLUSION: Intergenerational difference in educational achievements is decreased in patients with psychotic disorder and to a lesser extent in siblings of patients with psychotic disorder, and across higher levels of childhood urban exposure. More research is required to better understand the dynamics between early social and cognitive alterations in those at risk in relation to progress through the educational system and to understand the interaction between urban environment and educational outcomes.

Childhood trauma and childhood urbanicity in relation to psychotic disorder.

BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim of this study was twofold: (1) to investigate whether childhood urbanicity moderates the effect of childhood trauma, in a model predicting psychotic disorder; (2) to investigate whether there is an association between the urban environment and childhood trauma and whether this is moderated by genetic liability for psychotic disorder. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 1119) and 589 healthy controls from the Netherlands and Belgium were studied. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire Short Form. Urban exposure was defined at four levels, considering the population density, using data from Statistics Netherlands and the equivalent database in Belgium. RESULTS: There was a significant interaction between childhood urbanicity on the one hand and childhood trauma on the other, indicating that trauma was significantly associated with psychotic disorder, with increasing odds ratios for higher levels of childhood urbanicity. In addition, there was weak evidence that childhood urbanicity was associated with childhood trauma in the patient group: higher levels of childhood urbanicity were associated with higher trauma scores. CONCLUSION: The urban environment may moderate the risk-increasing effect of childhood trauma for psychotic disorder and childhood urbanicity may be a risk factor for childhood trauma in individuals who later develop psychotic disorder.

Evidence that childhood urban environment is associated with blunted stress reactivity across groups of patients with psychosis, relatives of patients and controls.

PURPOSE: Psychosis is associated with urban upbringing, and increased emotional reactivity is associated with psychosis. The aim of this study was to examine to what degree urban upbringing impacts emotional reactivity, and how this may be relevant for psychotic disorder and familial risk of psychotic disorder. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 57), 59 first degree relatives of patients and 75 healthy comparison subjects were studied with the experience sampling method (a random time sampling technique to assess affective experience in relation to fluctuating stressors in the flow of daily life), to measure a change in negative affect in relation to subjective stress. Urban exposure was defined at 5 levels, considering the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. RESULTS: Multilevel random regression analyses showed that urban upbringing was consistently and strongly associated with a reduced increase in negative affect in relation to SS in adulthood in a dose-response fashion in all three groups. Regression coefficients in the patient group decreased from 0.148 (p < 0.001) in the lowest urbanicity level to 0.094 (p < 0.001) in the highest urbanicity level. CONCLUSION: The findings suggest that urban upbringing may occasion "habituation" rather than "sensitization" across groups, which may or may not be relevant for the onset of psychotic disorder.

Social support and social rhythm regularity in elderly patients with major depressive disorder.

OBJECTIVE: According to the social zeitgeber theory, the lack of social support (SS) may decrease circadian rhythm regularity. However, the effect of SS on social rhythms in major depression has never been investigated. The objective of this study was to investigate the relation between SS and social rhythms in elderly patients with major depression. METHODS: Case-control study on the relation of SS with social rhythm regularity in 213 elderly patients with major depressive disorder (MDD) and 183 elderly healthy comparison subjects (HCs). Social rhythm regularity was studied using the social rhythm metric (SRM-5), in which a lower score represents less regularity. SS was assessed with the social support list (SSL). RESULTS: Patients with MDD displayed lower SRM-5 scores than HCs (4.94 ± 0.94 versus 5.38 ± 1.12; p = 0.003), as well as lower SSL-interactions (60.0 ± 13.7 versus 70.5 ± 11.6; p <0.001), higher SSL-discrepancies (56.3 ± 15.5 versus 39.4 ± 7.2; p <0.001), and higher SSL-negative interactions (11.0 ± 4.5 versus 8.9 ± 1.9; p <0.001). In HCs, social support was negatively correlated with SRM-5 (SSL-interactions, r = -0.30; SSL-discrepancies, r = -0.23; SSL-negative interactions, r = -0.44). In MDD, SS was not correlated with SRM-5 (all r ≤ 0.03; all p >0.05). CONCLUSIONS: Patients with MDD showed lower social rhythm regularity as well as lower measures of SS than HCs. In HCs, high SS was correlated with low social rhythm regularity, suggesting that increases in SS in combination with a healthy organization of circadian rhythms allow the social rhythms to become less rigid. Interestingly, in MDD, no correlation was found, suggesting that patients have a blunted response to social stimuli and may, therefore, benefit from treatment that increases the susceptibility to SS.

White matter microstructure and network-connectivity in emerging adults with subclinical psychotic experiences.

Group comparisons of individuals with psychotic disorder and controls have shown alterations in white matter microstructure. Whether white matter microstructure and network connectivity is altered in adolescents with subclinical psychotic experiences (PE) at the lowest end of the psychosis severity spectrum is less clear. DWI scan were acquired in 48 individuals with PE and 43 healthy controls (HC). Traditional tensor-derived indices: Fractional Anisotropy, Axial Diffusivity, Mean Diffusivity and Radial Diffusivity, as well as network connectivity measures (global/local efficiency and clustering coefficient) were compared between the groups. Subclinical psychopathology was assessed with the Community Assessment of Psychic Experiences (CAPE) and Montgomery-Åsberg Depression Rating Scale (MADRS) questionnaires and, in order to capture momentary subclinical expression of psychosis, the Experience Sampling Method (ESM) questionnaires. Within the PE-group, interactions between subclinical (momentary) symptoms and brain regions in the model of tensor-derived indices and network connectivity measures were investigated in a hypothesis-generating fashion. Whole brain analyses showed no group differences in tensor-derived indices and network connectivity measures. In the PE-group, a higher positive symptom distress score was associated with both higher local efficiency and clustering coefficient in the right middle temporal pole. The findings indicate absence of microstructural white matter differences between emerging adults with subclinical PE and controls. In the PE-group, attenuated symptoms were positively associated with network efficiency/cohesion, which requires replication and may indicate network alterations in emerging mild psychopathology.

Blended care in the treatment of subthreshold symptoms of depression and psychosis in emerging adults: A randomised controlled trial of Acceptance and Commitment Therapy in Daily-Life (ACT-DL).

In this study, the feasibility and efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), ACT augmented with a daily life application, was investigated in 55 emerging adults (age 16 to 25) with subthreshold depressive and/or psychotic complaints. Participants were randomized to ACT-DL (n = 27) or to active control (n = 28), with assessments completed at pre- and post-measurement and 6- and 12-months follow-up. It took up to five (ACT-DL) and 11 (control) months to start group-based interventions. Participants attended on average 4.32 out of 5 ACT-DL sessions. On the app, they filled in on average 69 (48%) of signal-contingent beep-questionnaires, agreed to 15 (41%) of offered beep-exercises, initiated 19 on-demand exercises, and rated ACT-DL metaphors moderately useful. Relative to active control, interviewer-rated depression scores decreased significantly in ACT-DL participants (p = .027). Decreases in self-reported depression, psychotic-related distress, anxiety, and general psychopathology did not differ between conditions. ACT-DL participants reported increased mean NA (p = .011), relative to active controls. Mean PA did not change in either group, nor did psychological flexibility. ACT-DL is a feasible intervention, although adaptations in future research may improve delivery of and compliance with the intervention. There were mixed findings for its efficacy in reducing subthreshold psychopathology in emerging adults. Dutch Trial Register no.: NTR3808.

Reward anticipation in individuals with subclinical psychotic experiences: A functional MRI approach.

Previous research in patients with psychotic disorder has shown widespread abnormalities in brain activation during reward anticipation. Research at the level of subclinical psychotic experiences in individuals unexposed to antipsychotic medication is limited with inconclusive results. Therefore, brain activation during reward anticipation was examined in a larger sample of individuals with subclinical psychotic experiences (PE). Participants in the PE-group were included based on CAPE scores. A sample of emerging adults aged 16-26 years (n = 47) with PE and healthy controls (HC) (n = 40) underwent fMRI scanning. The Monetary Incentive Delay task was conducted with cues related to win, loss or neutral conditions. fMRI nonparametric tests were used to examine the reward versus neutral cue contrast. A significant main effect of the large win (€3.00) > neutral contrast was found in both groups showing activation in many brain areas, including classic reward regions. Whole brain analysis on the group comparison regarding the large win > neutral contrast showed significantly decreased activation in the right insula, putamen and supramarginal gyrus in the PE-group compared to controls. There was no group difference in the hypothesized reward-related region. Decreased activation in the right insula, putamen and supramarginal gyrus during reward anticipation in individuals with PE may be consistent with altered processing of sensory information, related to decreased emotional valuing and motivational tendencies and/or altered motor-cognitive processes. The absence of group differences in striatal activation suggests that activation here is intact in the earliest stages of psychosis and may exhibit progressive deterioration in as the disease develops.

Clozapine Monotherapy as a Treatment for Antipsychotic-Induced Tardive Dyskinesia: A Meta-Analysis.

OBJECTIVE: Tardive dyskinesia (TD) is an antipsychotic-induced movement disorder that typically occurs after long-term exposure to antipsychotic drugs. There is evidence that switching to clozapine reduces TD. This meta-analysis reviews the effect of switching to clozapine on the severity of TD. DATA SOURCES: The PubMed, PsycINFO, and Embase databases were searched for clozapine, tardive dyskinesia, and related keywords. The search was restricted to articles written in English and Dutch, and it was last updated on October 13, 2015. STUDY SELECTION: Sixteen studies were included in the meta-analysis. Inclusion criteria were a diagnosis of schizophrenia or a related disorder, a switch to clozapine monotherapy, and reports of scores on a TD rating scale before and after the switch to clozapine. DATA EXTRACTION: Two independent investigators extracted the data. Data were converted to standardized mean change scores and analyzed in a random-effects model. RESULTS: A random-effects model showed that the overall effect of switching to clozapine was a significant reduction in TD (npatients = 1,060, d = -0.40, P < .01), especially in the 4 studies that investigated the severity of TD as a primary outcome (npatients = 48, d = -2.56, P = .02). CONCLUSIONS: The overall results show that clozapine treatment can yield a slight reduction in TD. The severity of TD was reduced greatly in patients with moderate to severe TD. In patients with minimal to mild TD, switching to clozapine seldom worsens TD and a trend toward reduction is seen. These results support that a switch to clozapine should be considered for patients with moderate to severe TD and/or patients who experience substantial discomfort due to TD.

Real-life validation of reduced reward processing in emerging adults with depressive symptoms.

Subclinical symptoms of depression are common in emerging adults. Anhedonia is one such symptom that specifically puts one at risk for developing clinical depression. Recently, important progress has been made in elucidating the underlying neurobiology of anhedonia. This progress rests on many experimental studies examining how subjects with depressive symptoms respond to anticipating and consuming rewarding stimuli. Translating these findings to real-life reward processing dynamics is an important next step in order to guide fine-tuning of preventive treatments. We propose that the Experience Sampling Methodology (ESM) represents a useful tool in addressing this issue. ESM requires individuals to carry a device that beeps at semirandom moments, inviting them to fill out a short questionnaire on mood, context, and behavior. Using this methodology, we aimed to decompose the construct of reward processing into its daily life dynamics, by investigating how positive affect (PA), reward anticipation and active behavior influence each other over time. A group of emerging adults (aged 16-25) was included, of which two-thirds presented with subclinical depressive symptoms. Associations between PA, reward anticipation and active behavior manifested in the flow of daily life. Depressive symptoms were significantly associated with reduced time-lagged associations between reward anticipation and active behavior (ß = -.005, p = .006) and active behavior and reward anticipation (ß = -.002, p = .027). The moderating effect of depressive symptoms on the time-lagged association between reward anticipation and PA approached significance (ß = -.002, p = .051). These findings represent an important step in translating experimental knowledge on reward processing into daily life processes. (PsycINFO Database Record

Behavioral pattern separation and its link to the neural mechanisms of fear generalization.

Fear generalization is a prominent feature of anxiety disorders and post-traumatic stress disorder (PTSD). It is defined as enhanced fear responding to a stimulus that bears similarities, but is not identical to a threatening stimulus. Pattern separation, a hippocampal-dependent process, is critical for stimulus discrimination; it transforms similar experiences or events into non-overlapping representations. This study is the first in humans to investigate the extent to which fear generalization relies on behavioral pattern separation abilities. Participants (N = 46) completed a behavioral task taxing pattern separation, and a neuroimaging fear conditioning and generalization paradigm. Results show an association between lower behavioral pattern separation performance and increased generalization in shock expectancy scores, but not in fear ratings. Furthermore, lower behavioral pattern separation was associated with diminished recruitment of the subcallosal cortex during presentation of generalization stimuli. This region showed functional connectivity with the orbitofrontal cortex and ventromedial prefrontal cortex. Together, the data provide novel experimental evidence that pattern separation is related to generalization of threat expectancies, and reduced fear inhibition processes in frontal regions. Deficient pattern separation may be critical in overgeneralization and therefore may contribute to the pathophysiology of anxiety disorders and PTSD.

Instrumental Assessment of Bradykinesia: A Comparison Between Motor Tasks.

Bradykinesia, a common symptom in psychiatry, is characterized by reduced movement speed and amplitude. Monitoring for bradykinesia is important, as it has been associated with reductions in quality of life and medication compliance. Subtle forms of bradykinesia have been associated with treatment response in antipsychotic-naïve first episode patients. Therefore, accurate and reliable assessment is of clinical importance. Several mechanical and electronic instruments have been developed for this purpose. However, their content validity is limited. This study investigated which tasks, or combinations thereof, are most suitable for assessing bradykinesia instrumentally. Eleven motor tasks were assessed using inertial sensors. Their capability of distinguishing bradykinetic patients with schizophrenia ( n = 6) from healthy controls ( n = 5) was investigated. Seven tasks significantly discriminated patients from controls. The combination of tasks considered most feasible for the instrumental assessment of bradykinesia was the gait, pronation/supination, leg agility and flexion/extension of elbow tasks (effect size = 2.9).

Reliability and validity of an instrument for the assessment of bradykinesia.

Bradykinesia is associated with reduced quality of life and medication non-compliance, and it may be a prodrome for schizophrenia. Therefore, screening/monitoring for subtle bradykinesia is of clinical and scientific importance. This study investigated the validity and reliability of such an instrument. Included were 70 patients with psychotic disorders. Inertial sensors captured mean cycle duration, amplitude and velocity of four movement tasks: walking, elbow flexion/extension, forearm pronation/supination and leg agility. The concurrent validity with the Unified Parkinson's Disease Rating Scale (UPDRS) bradykinesia subscale was determined using regression analysis. Reliability was investigated with the intra-class correlation coefficient. The duration, amplitude and velocities of the four tasks measured by the instrument explained 67% of the variance on the UPDRS bradykinesia subscale. The instrument test-retest reliability was high. The instrument investigated in this study is a valid and reliable alternative to observer-rated scales. It is an ideal tool for monitoring bradykinesia as it requires little training and experience to achieve reliable results.

The relation between depressive and obsessive-compulsive symptoms in obsessive-compulsive disorder: Results from a large, naturalistic follow-up study.

OBJECTIVE: Despite the frequent occurrence of depressive symptoms in obsessive-compulsive disorder (OCD), little is known about the reciprocal influence between depressive and obsessive-compulsive symptoms during the course of the disease. The aim of the present study is to investigate the longitudinal relationship between obsessive-compulsive and depressive symptoms in OCD patients. METHOD: We used the baseline and 1-year follow-up data of the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. In 276 patients with a lifetime diagnosis of obsessive-compulsive disorder, depressive and obsessive-compulsive symptoms were assessed at baseline and at one-year follow-up with the Beck Depression Inventory (BDI) and the Yale-Brown Obsessive Compulsive Symptom (Y-BOCS) scale. Relations were investigated using a cross-lagged panel design. RESULTS: The association between the severity of depressive symptoms at baseline and obsessive-compulsive symptoms at follow-up was significant (ß=0.244, p<0.001), while the association between the severity of obsessive-compulsive symptoms at baseline and depressive symptoms at follow-up was not (ß=0.097, p=0.060). Replication of the analyses in subgroups with and without current comorbid major depressive disorder (MDD) and subgroups with different sequence of onset (primary versus secondary MDD) revealed the same results. LIMITATIONS: There may be other factors, which affect both depressive and obsessive-compulsive symptoms that were not assessed in the present study. CONCLUSION: The present study demonstrates a relation between depressive symptoms and the course of obsessive-compulsive symptoms in OCD patients, irrespective of a current diagnosis of MDD and the sequence of onset of OCD and MDD.

Elevated salivary dehydroepiandrosterone-sulfate but normal cortisol levels in medicated depressed patients: preliminary findings.

Major depression is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In contrast to cortisol, dehydroepiandrosterone-sulfate (DHEA-S) has been less extensively studied in depressed patients. This study examined salivary morning and evening levels of cortisol and DHEA-S in 13 medicated, unipolar, non-psychotic depressed patients and 13 healthy volunteers. Diurnal declines in cortisol and DHEA-S levels were found in both depressed and control groups. In patients compared with controls, DHEA-S was significantly elevated, in conjunction with normal cortisol levels. Based on DHEA-S at 22:00 h only, 77% of the subjects were correctly classified in a discriminant analysis as depressed or control. When simultaneously entered in a multiple regression analysis, DHEA-S (morning and evening) and cortisol (evening only) predicted symptom severity in depressed patients. These preliminary results suggest that DHEA-S may be a more sensitive indicator of depression and symptom severity than cortisol in medicated but still clinically depressed patients.

Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies.

Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41,803) and 8 population-based cross-sectional studies (n = 35,546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34-3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90-3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12-4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17-3.47]). The estimated population attributable risk was 33% (16%-47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.