Background Schizophrenia is a heterogeneous disorder. Conflicting findings concerning abnormal levels of red blood cell fatty acids (RBC FA) in schizophrenia patients compared to healthy controls have been found. This stimulated research on the possible presence of a bimodal distribution of RBC FA. Bimodality suggests subgroups of the disease, including different endophenotypes and/or clinical characteristics. However, to date only a small number of publications reported on bimodality. The evidence whether fatty acids in red blood cells are bimodally distributed in schizophrenia is conflicting and data on bimodality in healthy controls are limited. The aim of current study was to investigate whether bimodal distributions of RBC FA concentrations are present in stable patients as compared to controls, and if so whether these distributions differ in form or size between patients and healthy controls. Methods From the GROUP study, a multisite, longitudinal, naturalistic cohort study, we investigated a subset of 215 patients, between 16 and 50 years, with a psychotic disorder and 98 healthy controls, between 16 and 50 years, for which RBC FA measurements were available. We studied a panel of 28 RBC FAs; 7 saturated fatty acids (SFAs), 9 monounsaturated fatty acids (MUFAs) and 12 polyunsaturated fatty acids (PUFAs). We did not investigate underlying genetics. The Likelihood Ratio Test was used to compare the goodness of fit of a bimodal or a unimodal distribution of each of the 28 FA concentrations. Hierarchical regressions were used to investigate whether belonging to the lower end of the distribution was associated with higher positive or negative symptom severity. Results At baseline, 19 out of 28 FAs are significantly bimodally distributed in patients versus 11 out of 28 FAs in controls (p < .05). As a group, RBC FAs in patients are borderline significant more often bimodally distributed as compared to controls. In contrast to previous studies, for AA, DHA and EPA we did not find a bimodal distribution in patients and an unimodal distribution in controls. Belonging to the lower end of the RBC FA distribution was not associated with positive or negative symptom severity. Conclusions Our findings do not support the existence of a unique bimodality of RBC FA distribution in relatively stable patients with schizophrenia spectrum disorders compared to controls. Bimodality may be more pronounced in the acute phase of the disease, further research into bimodality should focus on the influence of oxidative stress on levels of FAs and bimodality in (partly) remitted patients as well as acutely ill patients.

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.

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.

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.

ObjectivesCognitive 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.DesignCross‐sectional design with two groups (remitted MDD and controls).MethodsSixty‐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.ResultsLEIDS‐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).ConclusionsExisting 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.

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.

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.

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.

Background: A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant response, remain unknown.Purpose: To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response.Methods: We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N = 42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks).Results: Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study.Conclusion: Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in independent samples are needed to replicate and test the clinical applicability of these biological predictors for treatment response to result in a precision/personalized medicine approach for treatment. (C) 2017 Elsevier Ltd. All rights reserved.

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 78 days (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.

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.

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.

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.

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.

BACKGROUND:In the Netherlands the Boston psychiatric rehabilitation approach (bpr) is one of the most widely implemented rehabilitation methods. So far, little research has been done on the efficacy of this approach.AIM:To investigate the effect of bpr on the attainment of personal rehabilitation goals, social functioning and empowerment and on care requirements and quality of life in persons with severe mental illness (smi) in the Netherlands.METHOD:In a multicentre randomised controlled trial (rct:CLINICAL TRIAL REGISTRATION NUMBER:isrctn73683215) patients with smi were randomly assigned to bpr (n = 80) or 'care as usual' (cau; n = 76). The primary outcome was the attainment of the rehabilitation goal as formulated by the patient. The secondary outcomes were a change in the work situation and in the degree of independent living, in care requirements (Camberwell Assessment of Needs), in empowerment (Personal Empowerment Scale) and in the quality of life (who-qol). The effects were tested at 12 and 24 months.RESULTS:The degree of goal attainment was substantially higher in bpr at both 12 months (adjusted risk difference: 16%; 95%ci, 2 to 31; nnt = 7) and 24 months (adjusted risk difference: 21%, 95%ci, 4% to 38%; nnt = 5). The approach was also more effective in the area of societal participation (bpr: 21% adjusted increase, cau: 0% adjusted increase; nnt = 5), but not in the other secondary outcome measures.CONCLUSION:The results suggest that bpr is effective in supporting patients with smi to reach self-formulated rehabilitation goals and in enhancing their societal participation.

Background Cognitive impairments are an important feature of both remitted and depressed major depressive disorder (MDD) and bipolar disorder (BD). In particular, deficits in executive functioning may hamper everyday functioning. Identifying the neural substrates of impaired executive functioning would improve our understanding of the pathophysiology underlying these disorders, and may eventually aid in discriminating between MDD and BD, which is often difficult during depression and remission. To date, mostly medicated MDD and BD subjects have been investigated, which may have influenced results. Therefore, we investigated executive functioning in medication-free depressed and remitted MDD and BD subjects. Method We used the Tower of London (ToL) visuospatial planning task to assess behavioural performance and blood oxygen-level dependent responses in 35 healthy controls, 21 remitted MDD, 23 remitted BD, 19 depressed MDD and nine depressed BD subjects. Results Visuospatial planning per se was associated with increased frontostriatal activity in depressed BD compared to depressed MDD. In addition, post-hoc analyses indicated that visuospatial planning load was associated with increased parietal activity in depressed compared to remitted subjects, and BD compared to MDD subjects. Task performance did not significantly differ between groups. Conclusions More severely affected, medication-free mood disorder patients require greater parietal activity to perform in visuospatial planning, which may be compensatory to maintain relatively normal performance. State-dependent frontostriatal hyperactivity during planning may be a specific BD characteristic, providing clues for further characterization of differential pathophysiology in MDD v. BD. This could potentially provide a biomarker to aid in the differentiation of these disorders.

Background: Childhood trauma exposure (CTE) is frequently reported by those with substance use disorders (SUDs). SUDs also frequently co-occur with attention deficit hyperactivity disorder (ADHD).Objective: To investigate the role of childhood trauma exposure (CTE) in the presence and the persistence of ADHD'in treatment seeking SUD patients.Method: Data was derived from the International ADHD in Substance Use Disorder Prevalence (IASP) study. A structured interview was administered to 1274 treatment-seeking SUD patients aged 18 to 65.Results: CTE was present in 53.5% of the patients and comorbid adult ADHD in 14.1%. CTE was significantly associated with ADHD: the prevalence of adult ADHD with and without CTE was 19.4% and 8.5% (OR adjusted for age, gender, main substance of abuse, BPD, and ASPD 1.91 [95% C11.29-2.81]). CTE was not associated with the severity of adult ADHD or with the persistence of childhood ADHD into adulthood.Conclusions: CTE is common in SUD patients and associated with adult ADHD but not with the persistence of childhood ADHD into adulthood. These findings suggest that the increased rate of adult ADHD in SUD patients with CTE is not the consequence of a negative effect of CTE on:the persistence of childhood ADHD into adulthood, but a direct expression of the high rate of childhood ADHD in SUD patients with CTE. (C) 2016 Elsevier Ltd. All rights reserved.

Neuropeptide Y (NPY) and serotonergic systems have been implicated in the pathophysiology of depression but have not yet been linked together.In a randomized, double-blind crossover study, 28 medication-free patients with remitted depression and 26 healthy control subjects underwent tryptophan depletion (TD) and sham depletion. Plasma NPY concentrations were determined at baseline and at + 5, + 7, and + 24 h during TD and sham depletion, respectively. Hamilton Depression Rating Scale (HDRS, 24-item) scores were assessed at baseline and at + 7 and + 24 h after TD and sham depletion, respectively.There was no difference between healthy subjects and patients with remitted depression in baseline plasma NPY concentrations and in plasma NPY concentrations during TD and sham depletion, respectively. Plasma NPY concentrations did not differ between TD and sham depletion. At no time point there was an association between HDRS scores and plasma NPY concentrations in patients with remitted depression.Plasma NPY concentrations in rMDD patients were not obtained during the symptomatic phase of the illness. Only peripheral measurements of NPY were used.Decreased plasma NPY concentrations, as described previously during a spontaneous episode of major depression, appear as state but not as trait marker in depression. No evidence was found for an involvement of plasma NPY in relapse during TD. There appears no direct functional link between serotonergic neurotransmission and plasma NPY concentrations.