Delayed affective recovery to daily-life stressors signals a risk for depression.

OBJECTIVE: The aim of this study is to investigate the time to affective recovery from daily-life stressors between healthy controls (HC) and two groups with an increased risk for developing depression: individuals with subclinical symptoms of depression (SSD), and individuals remitted from a depressive episode with residual symptoms of depression (RRS). METHOD: The experience sampling method (ESM) was used to measure affective recovery to daily-life stressors. Affective recovery was defined as the moment that negative affect (NA) returned to baseline level following the first stressful event of the day. We assessed two different operationalizations of the baseline: NA at the moment before the stressful event (t-1), and mean-person NA. The effect of stress intensity, and cumulative stress were also assessed. RESULTS: Survival analyses showed significantly longer recovery times for the at risk groups in comparison to healthy individuals, albeit no significant difference was found between the two at risk groups (i.e. SSD and RRS). There was also an effect of cumulative stress, but not stress intensity on time to recovery in that cumulative stress resulted in significantly longer recovery times for all three groups. LIMITATIONS: The present study is limited by the ESM sampling design, assessments take place post-stress and therefore do not capture peak stress. Additionally, we are only able to assess patterns at the group level. Finally, there is a significant age difference between groups. CONCLUSION: Individuals at risk for depression display a delayed recovery to daily-life stressors when compared to healthy controls, which is not explained by differences in stress intensity or cumulative stress. Understanding what is driving this delay may help combat the development of depression.

Mentalization-based treatment for psychotic disorder: a rater-blinded, multi-center, randomized controlled trial.

BACKGROUND: Impaired mentalizing ability - an impaired ability to understand one's own and other people's behavior in terms of mental states - is associated with social dysfunction in non-affective psychotic disorder (NAPD). We tested whether adding mentalization-based treatment for psychotic disorder (MBTp) to treatment as usual (TAU) results in greater improvement in social functioning. METHODS: Multicenter, rater-blinded, randomized controlled trial. Eighty-four patients with NAPD were assigned to TAU or MBTp plus TAU. Patients in the MBTp group received 18 months of MBTp, consisting of weekly group sessions and one individual session per 2 weeks. Social functioning was measured using the Social Functioning Scale. We conducted ANCOVAs to examine the difference between treatment conditions directly after treatment and at 6-month follow-up and performed moderation and mediation analyses. RESULTS: Intention-to-treat analyses showed no significant differences between groups post-treatment (p = 0.31) but revealed the MBTp group to be superior to TAU at follow-up (p = 0.03). Patients in the MBTp group also seemed to perform better on measures of mentalizing ability, although evidence of a mediation effect was limited (p = 0.06). Lastly, MBTp treatment was less effective in chronic patients than in recent-onset patients (p = 0.049) and overall symptoms at baseline were mild, which may have reduced the overall effectiveness of the intervention. CONCLUSION: The results suggest that MBTp plus TAU may lead to more robust improvements in social functioning compared to TAU, especially for patients with a recent onset of psychosis.

Social functioning and subclinical psychosis in adolescence: a longitudinal general adolescent population study.

OBJECTIVES: To investigate the longitudinal relationship between subclinical psychotic symptoms and social functioning in a representative general population sample of adolescents. METHOD: Data were derived from a routine general health screening of 1909 adolescents in a circumscribed region. Baseline measurement was in the second grade of secondary school (T0), and follow-up occurred approximately 2 years later (T1). Social functioning and subclinical psychotic symptoms of hallucinations and delusions were assessed at both time points. RESULTS: Baseline (T0) social problems preceded follow-up (T1) subclinical delusions, but not T1 subclinical hallucinations. Similarly, T0 delusions preceded social problems at T1, but T0 hallucinations did not. CONCLUSION: This longitudinal general population study demonstrated a bidirectional association between social problems and delusions, but found no link between social problems and hallucinations. This may reflect a downward negative spiral where delusional thoughts and social problems reinforce each other.

Longitudinal associations between depression and diabetes complications: a systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of longitudinal studies assessing the bi-directional association between depression and diabetes macrovascular and microvascular complications. Embase, Medline and PsycINFO databases were searched from inception through 27 November 2017. A total of 4592 abstracts were screened for eligibility. Meta-analyses used multilevel random/mixed-effects models. Quality was assessed using the Newcastle-Ottawa scale. Twenty-two studies were included in the systematic review. Sixteen studies examined the relationship between baseline depression and incident diabetes complications, of which nine studies involving over one million participants were suitable for meta-analysis. Depression was associated with an increased risk of incident macrovascular (HR = 1.38; 95% CI: 1.30-1.47) and microvascular disease (HR = 1.33; 95% CI: 1.25-1.41). Six studies examined the association between baseline diabetes complications and subsequent depression, of which two studies involving over 230 000 participants were suitable for meta-analysis. The results showed that diabetes complications increased the risk of incident depressive disorder (HR = 1.14; 95% CI: 1.07-1.21). The quality analysis showed increased risk of bias notably in the representativeness of selected cohorts and ascertainment of exposure and outcome. Depression in people with diabetes is associated with an increased risk of incident macrovascular and microvascular complications. The relationship between depression and diabetes complications appears bi-directional. However, the risk of developing diabetes complications in depressed people is higher than the risk of developing depression in people with diabetes complications. The underlying mechanisms warrant further research.

Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder.

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

Mentalizing impairment as a mediator between reported childhood abuse and outcome in nonaffective psychotic disorder.

Reported childhood abuse has been linked to the severity of clinical symptoms and social dysfunction in non-affective psychotic disorder. Impaired mentalizing ability may be one of the mechanisms accounting for this effect. This study examined whether impaired mentalizing mediates the effect of reported childhood abuse on positive symptoms, negative symptoms, and social dysfunction. Eighty-seven patients with non-affective psychotic disorder were examined. Reported childhood abuse was measured using the Childhood Experience of Care and Abuse interview. Additionally, the Social Functioning Scale and the Positive and Negative Syndrome Scale were used. The Hinting Task was used to measure mentalizing impairment. Reported childhood abuse was significantly related to the severity of positive and negative symptoms, not to social dysfunction. Reported childhood abuse was also related to mentalizing impairment. Mentalizing impairment was related to negative symptoms, but not to positive symptoms or social dysfunction. Mentalizing impairment accounted for 40% of the association between reported childhood abuse and negative symptoms, indicating partial mediation. A sensitivity analysis revealed that the mediating effect was only observed in those who reported fairly severe childhood abuse.

Planning performance in schizophrenia patients: a meta-analysis of the influence of task difficulty and clinical and sociodemographic variables.

BACKGROUND: Despite a large body of research on planning performance in adult schizophrenia patients, results of individual studies are equivocal, suggesting either no, moderate or severe planning deficits. This meta-analysis therefore aimed to quantify planning deficits in schizophrenia and to examine potential sources of the heterogeneity seen in the literature. METHOD: The meta-analysis comprised outcomes of planning accuracy of 1377 schizophrenia patients and 1477 healthy controls from 31 different studies which assessed planning performance using tower tasks such as the Tower of London, the Tower of Hanoi and the Stockings of Cambridge. A meta-regression analysis was applied to assess the influence of potential moderator variables (i.e. sociodemographic and clinical variables as well as task difficulty). RESULTS: The findings indeed demonstrated a planning deficit in schizophrenia patients (mean effect size: ; 95% confidence interval 0.56-0.78) that was moderated by task difficulty in terms of the minimum number of moves required for a solution. The results did not reveal any significant relationship between the extent of planning deficits and sociodemographic or clinical variables. CONCLUSIONS: The current results provide first meta-analytic evidence for the commonly assumed impairments of planning performance in schizophrenia. Deficits are more likely to become manifest in problem items with higher demands on planning ahead, which may at least partly explain the heterogeneity of previous findings. As only a small fraction of studies reported coherent information on sample characteristics, future meta-analyses would benefit from more systematic reports on those variables.

Clinical high risk for psychosis: the association between momentary stress, affective and psychotic symptoms.

OBJECTIVE: The aim of this study was to assess associations between momentary stress and both affective and psychotic symptoms in everyday life of individuals at clinical high risk (CHR), compared to chronic psychotic patients and healthy controls, in search for evidence of early stress sensitization. It also assessed whether psychotic experiences were experienced as stressful. METHOD: The experience sampling method was used to measure affective and psychotic reactivity to everyday stressful activities, events and social situations in 22 CHR patients, 24 patients with a psychotic disorder and 26 healthy controls. RESULTS: Multilevel models showed significantly larger associations between negative affect (NA) and activity-related stress for CHR patients than for psychotic patients (P = 0.008) and for CHR compared to controls (P < 0.001). Similarly, the association between activity-related stress and psychotic symptoms was larger in CHR than in patients (P = 0.02). Finally, the association between NA and symptoms (P < 0.001) was larger in CHR than in patients. CONCLUSION: Stress sensitization seems to play a role particularly in the early phase of psychosis development as results suggest that CHR patients are more sensitive to daily life stressors than psychotic patients. In this early phase, psychotic experiences also contributed to the experience of stress.

CO2 exposure as translational cross-species experimental model for panic.

The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral-emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.

Daily life stress reactivity in remitted versus non-remitted depressed individuals.

BACKGROUND: Little is known about how daily life mood reactivity to minor stressors (stress reactivity) might change following major depressive disorder (MDD) treatment. We investigate whether (i) mood states and appraisals of daily stressors change after treatment; (ii) stress reactivity to event, activity, or social stress differs; (iii) stress reactivity depends on severity of residual depressive symptoms; and (iv) stress reactivity in individuals with remitted or non-remitted depression differ from that of never-depressed individuals. METHODS: Thirty depressed individuals participated in an experience sampling study before and after a treatment period of 18 months; 39 healthy individuals formed a comparison group. Reactivity of positive affect (PA) and negative affect (NA) to daily stressors were measured. RESULTS: More residual symptoms were associated with larger NA responses to stress. Compared to healthy controls, participants with non-remitted MDD showed higher NA-reactivity to all stressors. In contrast, stress reactivity to event and activity stressors was normalized in remitted patients. However, they still showed heightened NA-reactivity to social stress. CONCLUSIONS: Greater stress reactivity to event and activity stress appears to be state-dependent. The heightened social stress reactivity in remitted patients suggests that sensitivity to social stress may reflect an underlying vulnerability in MDD.

Exploring the underlying structure of mental disorders: cross-diagnostic differences and similarities from a network perspective using both a top-down and a bottom-up approach.

BACKGROUND: It has been suggested that the structure of psychopathology is best described as a complex network of components that interact in dynamic ways. The goal of the present paper was to examine the concept of psychopathology from a network perspective, combining complementary top-down and bottom-up approaches using momentary assessment techniques. METHOD: A pooled Experience Sampling Method (ESM) dataset of three groups (individuals with a diagnosis of depression, psychotic disorder or no diagnosis) was used (pooled N = 599). The top-down approach explored the network structure of mental states across different diagnostic categories. For this purpose, networks of five momentary mental states ('cheerful', 'content', 'down', 'insecure' and 'suspicious') were compared between the three groups. The complementary bottom-up approach used principal component analysis to explore whether empirically derived network structures yield meaningful higher order clusters. RESULTS: Individuals with a clinical diagnosis had more strongly connected moment-to-moment network structures, especially the depressed group. This group also showed more interconnections specifically between positive and negative mental states than the psychotic group. In the bottom-up approach, all possible connections between mental states were clustered into seven main components that together captured the main characteristics of the network dynamics. CONCLUSIONS: Our combination of (i) comparing network structure of mental states across three diagnostically different groups and (ii) searching for trans-diagnostic network components across all pooled individuals showed that these two approaches yield different, complementary perspectives in the field of psychopathology. The network paradigm therefore may be useful to map transdiagnostic processes.

Combining intensive practice nurse counselling or brief general practitioner advice with varenicline for smoking cessation in primary care: study protocol of a pragmatic randomized controlled trial.

INTRODUCTION: Combining behavioural support and pharmacotherapy is most effective for smoking cessation and recommended in clinical guidelines. Despite that smoking cessation assistance from the general practitioner can be effective, dissemination of clinical practice guidelines and efforts on upskilling has not lead to the routine provision of smoking cessation advice among general practitioners. Intensive counselling from the practice nurse could contribute to better smoking cessation rates in primary care. However, the effectiveness of intensive counselling from a practice nurse versus usual care from a general practitioner in combination with varenicline is still unknown. MATERIALS AND METHODS: A pragmatic randomized controlled trial was conducted comparing: (a) intensive individual counselling delivered by a practice nurse and (b) brief advice delivered by a general practitioner; both groups received 12-weeks of open-label varenicline. A minimum of 272 adult daily smoking participants were recruited and treated in their routine primary care setting. The primary outcome was defined as prolonged abstinence from weeks 9 to 26, biochemically validated by exhaled carbon monoxide. Data was analysed blinded according to the intention-to-treat principle and participants with missing data on their smoking status at follow-up were counted as smokers. Secondary outcomes included: one-year prolonged abstinence, short-term incremental cost-effectiveness, medication adherence, and baseline predictors of successful smoking cessation. DISCUSSION: This trial is the first to provide scientific evidence on the effectiveness, cost-effectiveness, and potential mechanisms of action of intensive practice nurse counselling combined with varenicline under real-life conditions. This paper explains the methodology of the trial and discusses the pragmatic and/or explanatory design aspects. TRIAL REGISTRATION: Dutch Trial Register NTR3067.

Childhood abuse and neglect in relation to the presence and persistence of psychotic and depressive symptomatology.

BACKGROUND: The association between childhood trauma and psychotic and depressive symptomatology is well established. However, less is known about the specificity and course of these symptoms in relation to childhood trauma. METHOD: In a large sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n = 1057) and controls (n = 589), multivariate (mixed-effects) regression analyses with multiple outcomes were performed to examine the association between childhood trauma and psychotic and depressive symptomatology over a 3-year period. RESULTS: A dose-response relationship was found between childhood trauma and psychosis. Abuse was more strongly associated with positive symptoms than with negative symptoms whereas the strength of the associations between neglect and positive and negative symptoms was comparable. In patients, similar associations between childhood trauma and psychotic or depressive symptoms were found, and in siblings and controls, stronger associations were found between trauma and depressive symptomatology. Childhood trauma was not related to a differential course of symptoms over a 3-year time period. CONCLUSIONS: In congruence with earlier work, our findings suggest that childhood trauma, and abuse in particular, is associated with (subthreshold) psychosis. However, childhood trauma does not seem to be associated with a differential course of symptoms, nor does it uniquely heighten the chance of developing (subthreshold) psychotic symptomatology. Our results indicate that trauma may instead contribute to a shared vulnerability for psychotic and depressive symptoms.

Childhood trauma is associated with a specific admixture of affective, anxiety, and psychosis symptoms cutting across traditional diagnostic boundaries.

BACKGROUND: Meta-analyses link childhood trauma to depression, mania, anxiety disorders, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life. METHOD: We used data from a representative general population sample (NEMESIS-2, n = 6646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP, n = 825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture. RESULTS: In NEMESIS-2, largely comparable associations were found between childhood trauma and depression, mania, anxiety and psychosis. However, childhood trauma was considerably more strongly associated with their lifetime admixture. These results were confirmed in the patient samples, in which it was consistently found that patients with a history of childhood trauma were more likely to have a combination of multiple symptom domains compared to their non-traumatized counterparts. This pattern was also found in exposed individuals who did not meet criteria for a psychotic, affective or anxiety disorder and who did not seek help for subclinical psychopathology. CONCLUSIONS: Childhood trauma increases the likelihood of a specific admixture of affective, anxiety and psychotic symptoms cutting across traditional diagnostic boundaries, and this admixture may already be present in the earliest stages of psychopathology. These findings may have significant aetiological, pathophysiological, diagnostic and clinical repercussions.

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the µ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

Effect of illness expression and liability on familial associations of clinical and subclinical psychosis phenotypes.

OBJECTIVE: Given the familial influences on schizophrenia, it may be hypothesized that specific symptom domains also cluster within families, and that this applies to both clinical and subclinical levels of expression. This hypothesis was put to the test in a group of patients with a DSM-IV diagnosis of psychotic disorder together with their unaffected siblings, and a group of healthy sib-pairs. METHOD: Subclinical positive, negative and depressive symptoms in relatives and healthy controls were assessed with the Community Assessment of Psychic Experiences (CAPE). Positive and negative schizotypy in relatives and controls was measured with the Structured Interview for Schizotypy-Revised. Multilevel linear regression analyses were conducted to investigate clustering of symptom dimensions within patient-relative sib-pairs (N = 811 pairs), healthy sib-pairs of affected families (N = 136 pairs) and healthy control sib-pairs (N = 58 pairs). RESULTS: Familial clustering of symptoms was found in all three groups. Effect sizes were largest in healthy control sib-pairs, smallest in patient-relative sib-pairs and intermediate in healthy sib-pairs of affected families. CONCLUSION: Studies of sibling associations in genetic studies of psychometric expression of psychosis liability need to take into account the fact that the higher levels of background genetic risk and presence of diagnosed illness are inversely associated with sibling associations.

Treatment for intermittent claudication and the effects on walking distance and quality of life.

The objective of the study was to provide an overview of the most common treatments for intermittent claudication and to determine the effectiveness in improving walking distance and quality of life based on a combination of direct and indirect evidence. We included trials that compared: angioplasty, surgery, exercise therapy or no treatment for intermittent claudication. Outcome measurements were walking distance (maximum, pain-free) and quality of life (physical, mental). We used a network meta-analysis model for the combination of direct and indirect evidence. We included 42 studies, presenting 3106 participants. The network meta-analysis showed that supervised exercise therapy (Δ = 1.62, P < 0.01), angioplasty (Δ = 1.89, P < 0.01) and surgery (Δ = 2.72, P = 0.02) increased walking distance significantly more than no treatment. Furthermore, supervised exercise therapy (Δ = 0.60, P < 0.01), angioplasty (Δ = 0.91, P = 0.01) and surgery (Δ = 1.07, P < 0.01) increased physical quality of life more than no treatment. However, in the sensitivity analysis, only supervised exercise therapy had additional value over no symptomatic treatment (Δ = 0.66, P < 0.01). In conclusion, this network meta-analysis indicates that supervised exercise therapy is more effective in both increasing walking distance and physical quality of life, compared with no treatment. Angioplasty and surgery also increase walking distance, compared with no treatment, but results for physical quality of life are less convincing.

The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis.

Different outcomes of the effect of catechin-caffeine mixtures and caffeine-only supplementation on energy expenditure and fat oxidation have been reported in short-term studies. Therefore, a meta-analysis was conducted to elucidate whether catechin-caffeine mixtures and caffeine-only supplementation indeed increase thermogenesis and fat oxidation. First, English-language studies measuring daily energy expenditure and fat oxidation by means of respiration chambers after catechin-caffeine mixtures and caffeine-only supplementation were identified through PubMed. Six articles encompassing a total of 18 different conditions fitted the inclusion criteria. Second, results were aggregated using random/mixed-effects models and expressed in terms of the mean difference in 24 h energy expenditure and fat oxidation between the treatment and placebo conditions. Finally, the influence of moderators such as BMI and dosage on the results was examined as well. The catechin-caffeine mixtures and caffeine-only supplementation increased energy expenditure significantly over 24 h (428.0 kJ (4.7%); P < 0.001 and 429.1 kJ (4.8%); P < 0.001, respectively). However, 24 h fat oxidation was only increased by catechin-caffeine mixtures (12.2 g (16.0%); P < 0.02 and 9.5 g (12.4%); P = 0.11, respectively). A dose-response effect on 24 h energy expenditure and fat oxidation occurred with a mean increase of 0.53 kJ mg(-1) (P < 0.01) and 0.02 g mg(-1) (P < 0.05) for catechin-caffeine mixtures and 0.44 kJ mg(-1) (P < 0.001) and 0.01 g mg(-1) (P < 0.05) for caffeine-only. In conclusion, catechin-caffeine mixtures or a caffeine-only supplementation stimulates daily energy expenditure dose-dependently by 0.4-0.5 kJ mg(-1) administered. Compared with placebo, daily fat-oxidation was only significantly increased after catechin-caffeine mixtures ingestion.

The effects of green tea on weight loss and weight maintenance: a meta-analysis.

INTRODUCTION: Different outcomes of the effect of green tea on weight loss (WL) and weight maintenance (WM) have been reported in studies with subjects differing in ethnicity and habitual caffeine intake. PURPOSE: To elucidate by meta-analysis whether green tea indeed has a function in body weight regulation. METHODS: English-language studies about WL and WM after green tea supplementation were identified through PubMed and based on the references from retrieved articles. Out of the 49 studies initially identified, a total of 11 articles fitted the inclusion criteria and provided useful information for the meta-analysis. Effect sizes (mean weight change in treatment versus control group) were computed and aggregated based on a random-effects model. The influence of several moderators on the effect sizes was examined. RESULTS: Catechins significantly decreased body weight and significantly maintained body weight after a period of WL (microcirc=-1.31 kg; P<0.001). Inhibition of this effect by high habitual caffeine intake (>300 mg per day) failed to reach significance (microcirc=-0.27 kg for high and microcirc=-1.60 kg for low habitual caffeine intake; P=0.09). Also, the seemingly smaller effect of catechins in Caucasian (microcirc=-0.82 kg) subjects compared with Asians (microcirc=-1.51 kg; P=0.37) did not reach significance. Interaction of ethnicity and caffeine intake was a significant moderator (P=0.04). CONCLUSIONS: Catechins or an epigallocatechin gallate (EGCG)-caffeine mixture have a small positive effect on WL and WM. The results suggest that habitual caffeine intake and ethnicity may be moderators, as they may influence the effect of catechins.