Effectiveness of a brief motivation enhancing intervention on treatment initiation, treatment retention and abstinence: Results from a multi-site cluster-randomized trial.

The aim of this study was to test the effectiveness of a brief motivational enhancing intervention (MEI) as an add-on to supervision-as-usual (SAU) in reducing time to treatment initiation in offenders with substance use disorders (SUDs) under probation supervision. We also tested the effectiveness in enhancing treatment retention and abstinence of primary substance rates. The study was designed as a multi-site, cluster randomized trial (CRT) in six addiction probation offices. We randomized 73 probation officers (37 to intervention, 36 to control) and followed 220 substance-abusing repeat offenders during their supervision (111 intervention, 109 control). Individualized SAU was compared with supervision with MEI. We report time to treatment initiation, treatment retention rate during the 12 months follow-up, and primary substance abstinence rate in the 30 days before follow-up. Results show that time to treatment initiation (χ2(1) = 1.817, p = .178), and the proportion of treatment retention (OR = 1.980, p = .213) and primary substance abstinence (OR = 0.945, p = .886) did not significantly differ between offenders that received SAU plus MEI and those that received SAU at 12 months follow-up. Our findings provide no evidence that supervision plus a brief manual-base MEI is more effective than SAU.

The Predictive Value of Impulsivity and Risk-Taking Measures for Substance Use in Substance Dependent Offenders.

Impulsivity and risk-taking are known to have an important impact on problematic substance use and criminal behavior. This study examined the predictive value of baseline self-report and behavioral impulsivity and risk-taking measures [Delay Discounting Task (DDT), Balloon Analogue Risk Task (BART) and Behavioral Inhibition, Behavioral Activation Scale (BIS/BAS)] in 12-months follow-up substance use outcomes (e.g., use of alcohol, cannabis and other substances) and criminal recidivism (yes/no). Participants were 213 male offenders with a substance use disorder (SUD) under probation supervision. Bivariate regression analyses showed that BIS and BAS levels were associated (respectively) with the use of alcohol and cannabis. Multiple regression analysis showed that BIS was negatively associated with alcohol use at follow-up, whereas cannabis use at baseline and BAS predicted cannabis use at follow-up. At a trend level, interactions between delay discounting and risk-taking, and interactions between baseline cannabis use and BAS and BART predicted cannabis use at follow-up. Other substance use at follow-up was solely predicted by baseline other substance use. Overall, the findings provide marginal support for the predictive utility of impulsivity and risk-taking in accounting for variability in substance use among offenders with a SUD. This may be partly explained by the fact that only a limited number of psychological factors was assessed in this study. The studied population consists of a severe group, in which relapse into substance use or criminal behavior likely is related to complex, interacting biopsychosocial factors, of which impulsivity measures play a relatively small part.

The Role of Motivation in Predicting Addiction Treatment Entry Among Offenders With Substance Use Disorders Under Probation Supervision.

Many offenders with a substance use disorder (SUD) do not enter addiction treatment. The aim of this study was to examine predictors of addiction treatment entry and to get more insight in the predictive value of treatment motivation. A total of 83 male offenders with a SUD under probation supervision in the Netherlands were assessed at the start of probation supervision and at 12-month follow-up. A total of 38 offenders (45.5%) entered addiction treatment in the follow-up period. Offenders with any mandated treatment (p = .028) and higher treatment motivation (p = .005) were more likely to enter treatment. Multiple logistic regression analysis showed that treatment motivation predicts addiction treatment entry in the first year of probation (OR = 2.215, p < .01). This emphasizes the relevance of treatment motivation for addiction treatment entry among offenders with a SUD. Pretreatment motivational interventions are therefore recommended for offenders with low motivation for treatment in probation settings.

Persistence and Subtype Stability of ADHD Among Substance Use Disorder Treatment Seekers.

Objective: To examine ADHD symptom persistence and subtype stability among substance use disorder (SUD) treatment seekers. Method: In all, 1,276 adult SUD treatment seekers were assessed for childhood and adult ADHD using Conners' Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; CAADID). A total of 290 (22.7%) participants met CAADID criteria for childhood ADHD and comprise the current study sample. Results: Childhood ADHD persisted into adulthood in 72.8% (n = 211) of cases. ADHD persistence was significantly associated with a family history of ADHD, and the presence of conduct disorder and antisocial personality disorder. The combined subtype was the most stable into adulthood (78.6%) and this stability was significantly associated with conduct disorder and past treatment of ADHD. Conclusion: ADHD is highly prevalent and persistent among SUD treatment seekers and is associated with the more severe phenotype that is also less likely to remit. Routine screening and follow-up assessment for ADHD is indicated to enhance treatment management and outcomes.

Correction: The use and helpfulness of self-management strategies for depression: The experiences of patients.

[This corrects the article DOI: 10.1371/journal.pone.0206262.].

The use and helpfulness of self-management strategies for depression: The experiences of patients.

OBJECTIVE: To explore which of 50 self-management strategies are actually used and which are perceived as most helpful by patients in their day-to-day management of depression, in order to empower patients and promote active engagement in their own care. METHODS: Retrospective study using an online self-report survey to assess the use and perceived helpfulness of 50 previously identified self-management strategies in 193 participants who recently recovered from a major depressive episode. RESULTS: Forty-five of the 50 strategies were used by at least half of all participants and about one third of all participants perceived almost 50% of all strategies as (very) helpful. The most used strategies, such as 'finding strategies to create pleasurable distractions', 'engaging in leisure activities' or 'identifying the cause of the depression', were not always perceived as most helpful. In addition, the perceived most helpful strategies, such as 'completing treatment' and 'leaving the house regularly' were not always the most used ones. CONCLUSIONS: Patients use and perceive a wide range of self-management strategies as helpful to recover from their depression. Patients use and perceive strategies about engagement in treatment and physical activities as being most helpful. These finding may contribute to the further development and implementation of self-management programs for the prevention or the rehabilitation of depression.

The measurement of cognitive reactivity to sad mood in patients remitted from major depressive disorder.

OBJECTIVES: Cognitive reactivity (CR) to sad mood is a risk factor for major depressive disorder (MDD). CR is usually measured by assessing change on the Dysfunctional Attitudes Scale (DAS-change) after sad mood-induction. It has, however, been suggested that the versions of the DAS (A/B) are not interchangeable, impacting the reliability and validity of the change score. The Leiden Index of Depression Sensitivity-Revised (LEIDS-R) is an alternative self-report measure of CR. Studies examining the relationship between LEIDS-R and DAS-change have shown mixed results. We examined whether scores of these CR measures differed between remitted MDD and controls, the relationship between these CR measures, and the effect of order of DAS administration on DAS-change. DESIGN: Cross-sectional design with two groups (remitted MDD and controls). METHODS: Sixty-eight MDD patients remitted from ≥2 previous episodes, not taking antidepressants, and 43 never-depressed controls participated in a mood-induction and filled in the DAS-A/B in randomized order before and after mood-induction, and LEIDS-R separately. RESULTS: LEIDS-R scores and pre-mood-induction DAS scores were significantly higher in remitted MDD than controls (p < .001, Cohen's d = 1.48; p = .001, Cohen's d = 0.66, respectively). DAS-change did not differ between these groups (p = .67, Cohen's d = 0.08). LEIDS-R correlated with DAS-change (r = .30, p = .042), but only in the group that filled in DAS-B before DAS-A. In remitted MDD, DAS-change was dependent on the order of DAS versions before and after mood-induction (10.6 ± 19.0 vs. -1.2 ± 10.5, for order B-A and A-B, respectively), with a significant group × order interaction (p = .012). CONCLUSIONS: Existing DAS versions are not interchangeable, which compromises the usefulness of mood-inductions in clinical practice. The LEIDS-R seems a valid measure of cognitive vulnerability to depression. PRACTITIONER POINTS: Clinical implications: Cognitive reactivity (CR) is a risk factor of depressive recurrence. The current measurement of CR, by assessing change on the Dysfunctional Attitudes Scale (DAS) after mood-induction, is not reliable. The Leiden Index Depression Sensitivity-Revised (LEIDS-R) is an alternative CR measure. In contrast to mood-induction, it reliably assesses depression vulnerability. The use of mood-inductions for clinical/research purposes is unnecessary. LIMITATIONS OF THE STUDY: We were not able to examine the effect of previous treatment, which could have affected results as psychological treatments probably have differential effects on CR. Examining un-medicated patients may have led to selection of a sample not completely representative for the general MDD population. We did not administer both parallel versions of the DAS (A/B) before and after mood-induction. This might have provided better understanding of their differential sensitivity to change.

Diagnosing ADHD during active substance use: Feasible or flawed?

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is highly prevalent in patients with a substance use disorder (SUD). Because of possible problems with validity, diagnostic assessment of ADHD is usually postponed until after a period of abstinence, which may jeopardize adequate and timely treatment. The aim of this study is to investigate how a diagnostic assessment of ADHD in patients who are actively using substances compares to the results of a second assessment after a period of full or partial abstinence. METHODS: Prospective test-retest study in a SUD treatment center among 127 treatment seeking adult SUD patients with a comorbid diagnosis of adult ADHD. Conners' Adult ADHD Diagnostic Interview for DSM-IV was administered at intake and after four SUD treatment sessions. RESULTS: The mean time interval between intake and retest assessment was 78days (SD=32; range 31-248). At the second ADHD assessment, substance use had decreased to about 50% of baseline consumption. Of the 127 patients with an initial diagnosis of ADHD, 121 patients (95.3%) still fulfilled DSM-IV adult ADHD criteria at re-diagnosis. Subtyping of ADHD was less stable (Cohen's Kappa=0.53). Agreement on the number of childhood and adult ADHD symptoms between both assessments was good (intraclass correlation coefficient of 0.69 and 0.65, respectively). Sensitivity analyses in subgroups of patients who were fully abstinent during the second assessment yielded very similar results. CONCLUSIONS: These findings strongly suggest that a pragmatic approach, in which patients are evaluated for ADHD even when they are not (yet) abstinent, is feasible and justifiable.

Advanced Glycation End Products in Recent-Onset Psychosis Indicate Early Onset of Cardiovascular Risk.

OBJECTIVE: Profoundly increased mortality rates in schizophrenia, largely caused by a higher risk and earlier onset of cardiovascular disease, remain a major challenge. During the human lifespan, advanced glycation end products (AGEs) accumulate, and their concentration is strongly linked to cardiovascular mortality. AGE accumulation can be accelerated by several pathways, including oxidative stress. METHODS: From March 2015 through January 2016, a case-control study including 111 patients with a recent-onset psychosis, 135 controls from a validation cohort, and 286 healthy controls was performed. Patients fulfilled the DSM-IV criteria for schizophrenia spectrum disorders with an illness duration shorter than 5 years. Main outcome parameters were skin autofluorescence levels of AGEs, controlled for age, gender, and smoking. Correlations of AGEs with cardiovascular risk factors and clinical variables were analyzed by hierarchical linear regression analyses. RESULTS: An AGE measurement was possible in 77.4% of cases. AGEs were elevated by 15.1% in recent-onset psychosis compared to healthy controls (P < .001), corresponding to an increased accumulation of AGEs normally occurring in approximately 10 years. AGEs were not related to traditional risk factors. However, duration of illness (P = .008), duration of antipsychotic treatment (P = .009), and cumulative exposure to antipsychotics (P = .023) correlated with AGEs. CONCLUSIONS: Patients with a recent onset of psychosis have increased AGE levels compared to healthy controls. These findings argue for an earlier implementation of treatment strategies aimed at preventing cardiovascular disease. Also, low-dose strategies of antipsychotics in schizophrenia could beneficially influence AGE levels.

Nursing Staff Factors Contributing to Seclusion in Acute Mental Health Care - An Explorative Cohort Study.

BACKGROUND: Seclusion is a controversial intervention. Efficacy with regard to aggressive behaviour has not been demonstrated, and seclusion is only justified for preventing safety hazards. Previous studies indicate that nursing staff factors may be predictors for seclusion, although methodological issues may have led to equivocal results. OBJECTIVE: To perform a prospective cohort study to determine whether nursing staff characteristics are associated with seclusion of adult inpatients admitted to a closed psychiatric ward. METHOD: We studied the association between nurses' demographics and incidence of seclusion during every shift. Data were collected during five months in 2013. Multiple logistic regression was used for analysis. RESULTS: In univariable analysis, we found a non-significant association between seclusion and female gender, odds ratio (OR) = 5.27 (0.98-28.49) and a significant association between seclusion and nurses' large physical stature, OR = 0.21 (0.06-0.72). We found that physical stature is the most substantial factor, although not significant: ORadjusted = 0.27 (0.07-1.04). CONCLUSION: Nurses' gender may be a predictor for seclusion, but it seems to be mediated by the effect of physical stature. We used a rigorous, census-based, prospective design to collect data on a highly detailed level and found a large effect of physical stature of nurses on seclusion. We found nurses' physical stature to be the most substantial predictor for seclusion. These and other factors need to be explored in further research with larger sample size.

Helpful Factors in the Treatment of Depression from the Patient's, Carer's and Professional's Perspective: A Concept Map Study.

OBJECTIVE: Depression research has resulted in knowledge about neurobiology, pharmacological strategies and short-term cost-effective treatments. However, more than two-thirds of all depressed patients experience insufficient improvement. Therefore, a better understanding of what patients, carers and professionals perceive as most helpful in the treatment of depression is needed. METHODS: Concept mapping, a mixed-method design, was used to identify the patients (n = 33), carers (n = 22) and professionals (n = 50) perspectives. In six brainstorm sessions, the patients, carers and professionals generated 795 ideas, which were condensed into 55 unique statements. Subsequently, 100 participants prioritized and sorted these statements, which were analysed by multidimensional scaling and cluster analysis and visualized as a two-dimensional map. RESULTS: The 55 statements were clustered in 10 factors and further grouped into four main-factors (meta-clusters): 'Professional therapist', 'Treatment content', 'Structured treatment process' and 'Treatment organisation'. Patients and carers prioritized 'Treatment organisation' higher than professionals, but overall there was considerable agreement about the factors of treatment the participants perceived as most helpful including factors related to the therapeutic relationship and the 'creation of hope'. CONCLUSIONS: Our study identified factors of depression treatment perceived as helpful according to patients, carers and professionals. Findings suggest that in a scientific era with emphasis on biological psychiatry, not only patients and carers, but also professionals consider aspecific factors the most helpful. Further studies might show that factors we found to be helpful in the treatment for depression, can be generalized to mental health treatment in general.

Early Nonresponse in the Antipsychotic Treatment of Acute Mania: A Criterion for Reconsidering Treatment? Results From an Individual Patient Data Meta-Analysis.

OBJECTIVE: To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treatment failure and, if so, to establish the best definition or criterion of an early nonresponse. DATA SOURCES: Short-term efficacy studies assessing antipsychotics that were submitted to the Dutch Medicines Evaluation Board during an 11-year period as part of the marketing authorization application for the indication of acute manic episode of bipolar disorder. Pharmaceutical companies provided their raw patient data, which enabled us to perform an individual patient data meta-analysis. STUDY SELECTION: All double-blind, randomized, placebo-controlled trials assessing the efficacy of antipsychotics for acute manic episode of bipolar disorder were included (10 trials). DATA EXTRACTION: All patients with data available for completer analysis (N = 1,243), symptom severity scores on the Young Mania Rating Scale (YMRS) at weeks 0, 1, and 2 and at study end point (week 3 or 4). RESULTS: The a priori chances of nonresponse and nonremission at study end point were 40.9% (95% CI, 38.2%-43.6%) and 65.3% (95% CI, 62.0%-68.6%), respectively. Early nonresponse in weeks 1 and 2, defined by cutoff scores ranging from a ≤ 10% to a ≤ 50% reduction in symptoms compared to baseline on the YMRS, significantly predicted nonresponse (≤ 0% symptom reduction) and nonremission (YMRS score higher than 8) in week 3. The predictive value of early nonresponse (PVnr_se) at week 1 for both nonresponse and nonremission at study end point declined linearly with increasing cutoff scores of early nonresponse; nonresponse: 76.0% (95% CI, 69.7%-82.3%) for a ≤ 10% response to 48.7% (95% CI, 45.5%-51.9%) for a ≤ 50% response; nonremission: 92.2% (95% CI, 88.3%-96.1%) for a ≤ 10% response to 76.8% (95% CI, 74.4%-79.5%) for a ≤ 50% response. A similar linear decline was observed for increasing cutoff scores of early nonresponse at week 2 for nonresponse, but not for nonremission at end point: nonresponse 90.3% (95% CI, 84.6%-96.0%) for a ≤ 10% response to 65.0% (95% CI, 61.4%-68.6%) for a ≤ 50% response; nonremission: 94.2% (95% CI, 89.7%-98.7%) for a ≤ 10% response and 93.2% (95% CI, 93.1%-95.1%) for a ≤ 50% response. Specific antipsychotic characteristics did not modify these findings at either time point (week 1: P = .127; week 2: P = .213). CONCLUSIONS: When patients fail to respond early (1-2 weeks) after the initiation of antipsychotic treatment for acute mania, clinicians should reconsider their treatment choice using a 2-stage strategy.

Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands.

BACKGROUND: Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual patients, but it is expensive and not reimbursed by the health insurance. OBJECTIVES: This study evaluates the support for abstinence oriented treatment among heroin-dependent patients and the acceptability of XRNT injections by heroin-dependent patients and treatment providers in The Netherlands. METHODS: A sample of 261 patients in methadone maintenance treatment or heroin assisted treatment and a sample of 188 addiction treatment providers completed specially designed questionnaires. RESULTS: The current study shows that many patients in opioid maintenance treatment (58%) report a desire to become abstinent from opioids and that 83% of the patients with a desire for abstinence are interested in XRNT. The majority of treatment providers (81%) are willing to support the prescription of XRNT injections in opioid-dependent patients to prevent relapse after detoxification. CONCLUSIONS: The current practice of automatic and indefinite continuation of opioid substitution should therefore be reconsidered. However, XRNT injections are very expensive and currently not reimbursed by the health insurance agencies in The Netherlands and thus not really available to most patients.

Vulnerability for new episodes in recurrent major depressive disorder: protocol for the longitudinal DELTA-neuroimaging cohort study.

INTRODUCTION: Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission. METHODS AND ANALYSIS: In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35-65 years) with ≥ 2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5 years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3 T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination. ETHICS AND DISSEMINATION: The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings. TRIAL REGISTRATION NUMBER: NTR3768.

Levels of Red Blood Cell Fatty Acids in Patients With Psychosis, Their Unaffected Siblings, and Healthy Controls.

BACKGROUND: Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder. METHODS: For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups. RESULTS: Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings. CONCLUSIONS: We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients.

Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?: An Individual Patient Data Regression Meta-Analysis.

Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight.

Association between olfactory identification and parkinsonism in patients with non-affective psychosis.

AIM: Olfactory identification deficits (OIDs) are seen in schizophrenia patients and individuals at increased risk for psychosis but its pathophysiology remains unclear. Although dopaminergic imbalance is known to lie at the core of schizophrenia symptomatology, its role in the development of OIDs has not been elucidated yet. This study investigated the association between OIDs and symptoms of parkinsonism as a derivative of dopaminergic functioning. METHODS: In 320 patients diagnosed with non-affective psychosis, olfactory identification performance was assessed by means of the Sniffin' Sticks task. Level of parkinsonian symptoms was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS-III). By means of multiple linear regression with bootstrapping, the association between UPDRS and Sniffin' Sticks score was investigated while correcting for potential confounders. A Bonferroni corrected P-value of 0.007 was used. RESULTS: Higher UPDRS scores significantly predicted worse olfactory identification in patients with non-affective psychosis with an unadjusted b = -0.07 (95% CI -0.10 to -0.04) and an adjusted b = -0.04 (95% CI -0.07 to -0.01). CONCLUSION: Results provide preliminary evidence that the same vulnerability may underlie the development of parkinsonism and OIDs in patients with non-affective psychosis. Further investigation should evaluate the clinical value of OIDs as a marker of dopaminergic vulnerability that may predict psychosis.

Cognitive reactivity versus dysfunctional cognitions and the prediction of relapse in recurrent major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD) is a burdensome disease that has a high risk of relapse/recurrence. Cognitive reactivity appears to be a risk factor for relapse. It remains unclear, however, whether dysfunctional cognitions alone or the reactivity of such cognitions to mild states of sadness (ie, cognitive reactivity) is the crucial factor that increases relapse risk. We aimed to assess the long-term predictive value of cognitive reactivity versus dysfunctional cognitions and other risk factors for depressive relapse. METHOD: In a prospective cohort of outpatients (N = 116; studied between 2000-2005) who had experienced ≥ 2 previous major depressive episodes (MDEs) and were in remission (DSM-IV) at the start of follow-up, we measured cognitive reactivity, with the Leiden Index of Depression Sensitivity (LEIDS), and dysfunctional cognitions, with the Dysfunctional Attitudes Scale, simultaneously. Course of illness (with the primary outcome of MDE assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) and time to relapse were monitored prospectively for 3.5 years. RESULTS: Cognitive reactivity scores were associated with time to relapse over the 3.5-year follow-up and also when corrected for the number of previous MDEs and concurrent depressive symptoms (hazard ratio for 1 standard deviation [(HR(SD)); 20 points of the LEIDS, measuring cognitive reactivity] = 1.47; 95% CI, 1.04-2.09; P = .031). Rumination appeared to be a particularly strong predictor of relapse (HR(SD) = 1.60; 95% CI, 1.13-2.26; P = .007). Dysfunctional cognitions did not predict relapse over 3.5 years (HR(SD) = 1.00; 95% CI, 0.74-1.37; P = .93). Every 20-point increase on the cognitive reactivity scale resulted in a 10% to 15% increase in risk of relapse (corrected for previous MDEs and concurrent depressive symptoms). CONCLUSIONS: Cognitive reactivity--and particularly rumination--is a long-term predictor of relapse. Future research should address whether psychological interventions can improve cognitive reactivity scores and thereby prevent depressive relapses. TRIAL REGISTRATION: ISRCTN Identifier: 68246470.

Erythrocyte fatty acid profiles and plasma homocysteine, folate and vitamin B6 and B12 in recurrent depression: Implications for co-morbidity with cardiovascular disease.

Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD.