The National Institute of Mental Health launched the Research Domain Criteria (RDoC) initiative to better understand dimensions of behavior and identify targets for treatment. Examining dimensions across psychiatric illnesses has proven challenging, as reliable behavioral paradigms that are known to engage specific neural circuits and translate across diagnostic populations are scarce. Delay discounting paradigms seem to be an exception: they are useful for understanding links between neural systems and behavior in healthy individuals, with potential for assessing how these mechanisms go awry in psychiatric illnesses. This article reviews relevant literature on delay discounting (or the rate at which the value of a reward decreases as the delay to receipt increases) in humans, including methods for examining it, its putative neural mechanisms, and its application in psychiatric research. There exist rigorous and reproducible paradigms to evaluate delay discounting, standard methods for calculating discount rate, and known neural systems probed by these paradigms. Abnormalities in discounting have been associated with psychopathology ranging from addiction (with steep discount rates indicating relative preference for immediate rewards) to anorexia nervosa (with shallow discount rates indicating preference for future rewards). The latest research suggests that delay discounting can be manipulated in the laboratory. Extensively studied in cognitive neuroscience, delay discounting assesses a dimension of behavior that is important for decision-making and is linked to neural substrates and to psychopathology. The question now is whether manipulating delay discounting can yield clinically significant changes in behavior that promote health. If so, then delay discounting could deliver on the RDoC promise.

Altered resting-state functional connectivity (rsFC) has been noted in large-scale functional networks in attention-deficit/hyperactivity disorder (ADHD). However, identifying consistent abnormalities of functional networks is difficult due to varied methods and results across studies. To integrate rsFC alterations and search for coherent patterns of intrinsic functional network impairments in ADHD, this research conducts a coordinate-based meta-analysis of voxel-wise seed-based rsFC studies comparing rsFC between ADHD patients and healthy controls. A total of 25 datasets from 21 studies including 700 ADHD patients and 580 controls were analyzed. We extracted the coordinates of seeds and between-group effects. Each seed was then categorized into a seed-network by its location within priori 7-network parcellations. Then, pooled meta-analyses were conducted for the default mode network (DMN), frontoparietal network (FPN) and affective network (AN) separately, but not for the ventral attention network (VAN), dorsal attention network (DAN), somatosensory network (SSN) and visual network due to a lack of primary studies. The results showed that ADHD was characterized by hyperconnectivity between the FPN and regions of the DMN and AN as well as hypoconnectivity between the FPN and regions of the VAN and SSN. These findings not only support the triple-network model of pathophysiology associated with ADHD but also extend this model by highlighting the involvement of the SSN and AN in the mechanisms of network interactions that may account for motor hyperactivity and impulsive symptoms.

There is an enormous interest in identifying the causes of psychiatric disorders but there are considerable challenges in identifying which risks are genuinely causal. Traditionally risk factors have been inferred from observational designs. However, association with psychiatric outcome does not equate to causation. There are a number of threats that clinicians and researchers face in making causal inferences from traditional observational designs because adversities or exposures are not randomly allocated to individuals. Natural experiments provide an alternative strategy to randomized controlled trials as they take advantage of situations whereby links between exposure and other variables are separated by naturally occurring events or situations. In this review, we describe a growing range of different types of natural experiment and highlight that there is a greater confidence about findings where there is a convergence of findings across different designs. For example, exposure to hostile parenting is consistently found to be associated with conduct problems using different natural experiment designs providing support for this being a causal risk factor. Different genetically informative designs have repeatedly found that exposure to negative life events and being bullied are linked to later depression. However, for exposure to prenatal cigarette smoking, while findings from natural experiment designs are consistent with a causal effect on offspring lower birth weight, they do not support the hypothesis that intra-uterine cigarette smoking has a causal effect on attention-deficit/hyperactivity disorder and conduct problems and emerging findings highlight caution about inferring causal effects on bipolar disorder and schizophrenia.

To what extent meditation techniques (which incorporate practices to regulate attention, construct individual values, or deconstruct self-related assumptions), are more or less effective than relaxation therapy in the treatment of anxiety, is not clear. The aim of this study was to examine the effectiveness of meditation compared to relaxation in reducing anxiety. A systematic review from PubMed, Embase, PsycInfo and the Cochrane Central was conducted. A meta-analysis of 14 RCTs (n = 862 participants suffering from anxiety disorders or high trait anxiety) was performed. Effect sizes (ESs) were determined by Hedges’ g. Heterogeneity, risk of publication bias, quality of studies/interventions, and researcher allegiance, were evaluated. Meditation techniques incorporated attentional elements, and five of them also added constructive practices. No studies were found using deconstructive exercises. The overall ES was g = −0.23 [95% confidence interval (CI) −0.40 to −0.07], favouring meditation (number needed to treat = 7.74). Heterogeneity was low (I2 = 2; 95% CI 0 to 56). There was no evidence of publication bias, but few studies and interventions were of high quality, and allegiance might be moderating results. Meditation seems to be a bit more effective than relaxation in the treatment of anxiety, and it might also remain more effective at 12-month follow-up. However, more research using the full spectrum of meditation practices to treat different anxiety disorders, including independent studies to avoid researcher allegiance, is needed if we are to have a precise idea of the potential of these techniques compared to relaxation therapy.

Several studies have demonstrated a vicious cycle of violence, in which experiences of childhood maltreatment (CM) transition into later perpetration of aggressive acts. But evidence for the presence of this cycle in adult women is mixed. The aim of this meta-analysis is to investigate the strength of associations and the mechanisms underlying a cycle of violence in women. Databases were searched for terms related to female aggression, violence, delinquency, antisocial behavior, or offending in addition to exposure to traumatic experiences, abuse, or maltreatment during childhood. Only peer-reviewed studies were included that investigated associations between any type of CM and different acts of aggression. Multi-level meta-analyses were applied, as well as meta-regressions, all based on Cohen's d. K = 34 studies were identified. The overall association between exposure to CM was in the positive but small range (Cohen's d = 0.30). There was no significant difference between specific types of abuse and/or neglect. However, associations were smaller for the perpetration of sexual aggression and violent crime compared with other acts of aggression. These findings underline the long-lasting and devastating impact of CM, including types of maltreatment that were long assumed to be less severe. Due to the limited number of available studies, interactions between types of CM and aggression could not be modeled, thus compromising their probable interacting contribution to the cycle of violence. Early interventions targeting families and women at risk are critical in order to prevent ongoing cycles of violence.

Despite substantial advances in treatment and management strategies for major depression, less than 50% of patients respond to first-line antidepressant treatment or psychotherapy. Given the growing number of controlled studies of psychotherapy for treatment-resistant depression (TRD) and the preference for psychotherapy of depressed subjects as a treatment option, we conducted a meta-analysis and meta-regression analysis to investigate the effectiveness of psychotherapy for TRD. Seven different psychotherapies were studied in 21 trials that included a total of 25 comparisons. In three comparisons of psychotherapy v. treatment as usual (TAU) we found no evidence to conclude that there is a significant benefit of psychotherapy as compared with TAU. In 22 comparisons of add-on psychotherapy plus TAU v. TAU only, we found a moderate general effect size of 0.42 (95% CI 0.29–0.54) in favor of psychotherapy plus TAU. The meta-regression provided evidence for a positive association between baseline severity as well as group v. individual therapy format with the treatment effect. There was no evidence for publication bias. Most frequent investigated treatments were cognitive behavior therapy, interpersonal psychotherapy, mindfulness-based cognitive therapy, and cognitive behavioral analysis system of psychotherapy. Our meta-analysis provides evidence that, in addition to pharmacological and neurostimulatory treatments, the inclusion of add-on of psychotherapy to TAU in guidelines for the treatment of TRD is justified and will provide better outcomes for this difficult-to-treat population.

Depression and a number of other psychiatric conditions can impair cognition and give the appearance of neurodegenerative disease. Collectively, this group of disorders is known as ‘pseudodementia’ and are important to identify given their potential reversibility with treatment. Despite considerable interest historically, the longitudinal outcomes of patients with pseudodementia remain unclear. We conducted a systematic review of longitudinal studies of pseudodementia. Bibliographic databases were searched using a wide range of search terms. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 18 studies with follow-up varying from several weeks to 18 years. Overall, 284 patients were studied, including 238 patients with depression, 18 with conversion disorder, 14 with psychosis, and 11 with bipolar disorder. Irrespective of diagnosis, 33% developed irreversible dementia at follow-up, 53% no longer met criteria for dementia, and 15% were lost to follow-up. Considerable variability was identified, with younger age at baseline, but not follow-up duration, associated with better outcomes. ECT and pharmacological interventions were also reported to be beneficial, though findings were limited by the poor quality of the studies. Overall, the findings suggest that pseudodementia may confer an increased risk of irreversible dementia in older patients. The findings also indicate, however, that a significant proportion improve, while many remain burdened with their psychiatric condition, independent of organic dementia. The findings support the clinical value of the construct and the need for its re-examination in light of developments in neuroimaging, genomics, other investigative tools, and trial methodology.

To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.

Recently, there has been renewed interest in the application of assumptions from complex systems theory in the field of psychopathology. One assumption, with high clinical relevance, is that sudden transitions in symptoms may be anticipated by rising instability in the system, which can be detected with early warning signals (EWS). Empirical studies support the idea that this principle also applies to the field of psychopathology. The current manuscript discusses whether assumptions from complex systems theory can additionally be informative with respect to the specific symptom dimension in which such a transition will occur (e.g. whether a transition towards anxious, depressive or manic symptoms is most likely). From a complex systems perspective, both EWS measured in single symptom dynamics and network symptom dynamics at large are hypothesized to provide clues regarding the direction of the transition. Challenging research designs are needed to provide empirical validation of these hypotheses. These designs should be able to follow sudden transitions ‘live’ using frequent observations of symptoms within individuals and apply a transdiagnostic approach to psychopathology. If the assumptions proposed are supported by empirical studies then this will signify a large improvement in the possibility for personalized estimations of the course of psychiatric symptoms. Such information can be extremely useful for early intervention strategies aimed at preventing specific psychiatric problems.

Psychotic symptoms (PS) are experienced by a substantial proportion of the general population. When not reaching a threshold of clinical relevance, these symptoms are defined as psychotic experiences (PEs) and may exist on a continuum with psychotic disorders. Unfavorable socio-environmental conditions, such as ethnic minority position (EMP) and migrant status (MS), may increase the risk of developing PS and PEs. We conducted an electronic systematic review and a meta-analysis assessing the role of EMP and MS for the development and persistence of PS in the general population. Sub-group analyses were performed investigating the influence of ethnic groups, host countries, age, types of PS, and scales. Twenty-four studies met our inclusion criteria. EMP was a relevant risk factor for reporting PS [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.22–1.70) and PEs (OR 1.36, 95% CI 1.16–1.60). The greatest risk was observed in people from the Maghreb and the Middle East ethnic groups in Europe (OR 3.30, 95% CI 2.09–5.21), in Hispanic in the USA (OR 1.98, 95% CI 1.43–2.73), and in the Black populations (OR 1.85, 95% CI 1.39–2.47). We found a significant association between MS and delusional symptoms (OR 1.47, 95% CI 1.33–1.62). We found no association between EMP and persistence of PEs.

EMP was associated with increased risk of reporting PS and PEs, and the risk was higher in ethnic groups facing deprivation and discrimination. We found an association between MS and delusional symptoms. These results raise questions about the precise role of socio-environmental factors along the psychosis continuum.

Available twin-family data on sex differences in antisocial behavior (ASB) simultaneously suggest that ASB is far more prevalent in males than in females, and that its etiology (i.e. the effects of genes, environments, hormones, culture) does not differ across sex. This duality presents a conundrum: How do we make sense of mean sex differences in ASB if not via differences in genes, environments, hormones, and/or cultures? The current selective review and critique explores possible contributions to these seemingly incompatible sets of findings. We asked whether the presence of sex differences in behavior could be smaller than is typically assumed, or confined to a specific set of behaviors. We also asked whether there might be undetected differences in etiology across sex in twin-family studies. We found little evidence that bias or measurement invariance across sex account for phenotypic sex differences in ASB, but we did identify some key limitations to current twin-family approaches. These included the questionable ability of qualitative sex difference analyses to detect gender norms and prenatal exposure to testosterone, and concerns regarding specific analytic components of quantitative sex difference analyses. We conclude that the male preponderance in ASB is likely to reflect a true sex difference in observed behavior. It was less clear, however, that the genetic and environmental contributions to ASB are indeed identical across sex, as argued by prior twin-family studies. It is our hope that this review will inspire the development of new, genetically-informed methods for studying sex differences in etiology.

The negative symptoms of psychosis and depressive symptomatology share several features, e.g. low motivation, apathy and reduced activity. Understanding the associations between these two sets of symptoms will support improved assessment and the development of interventions targeting these difficulties in people with psychosis. This is the first large systematic review and meta-analysis to quantify the relationship between these two categories of symptoms, as measured in studies to date. PsycInfo, Embase and Medline were systematically searched to identify eligible studies. Inclusion criteria ensured the studies measured both depression and negative symptoms using validated measures in a sample of over 8000 participants with non-affective psychosis diagnoses. The search led to 2020 records being screened and 56 included in the meta-analysis and review. Both meta-analyses and meta-regressions were conducted to explore the main effect and potential moderating variables. A clear pattern emerges showing that higher ratings of negative symptoms are associated with higher levels of depressive symptoms, with a small effect [standardised effect size = 0.19, p < 0.05). This did not vary greatly with the measures used (SES = 0.19–0.26) and was not moderated by demographic variables or quality ratings. Interestingly, higher depressive symptoms predict a significant relationship with co-occurring negative symptoms. However, higher negative symptoms predict that it is less likely there will be a relationship with co-occurring depressive symptoms. Heterogeneity was high across these analyses. The findings support the adoption of a symptom-specific approach to understanding the interplay between negative and depressive symptoms in psychosis, to improve assessment and intervention.