Previous research has shown the utility of imaging measures of neural activity in identifying deficits in cognitive functioning in individuals with a history of child abuse. The purpose of the present study was to measure differences that may exist between individuals who reported physical, emotional, or sexual abuse as children (n = 37) vs. those who did not (n = 47) using Functional Near Infrared Spectroscopy (fNIRS) during the completion of cognitive tasks of executive function. The results showed a significantly higher rate and number of errors of commission on the Conners CPT test in the child abuse group compared to the control group. The analyses also showed a statistically significant decrease in oxyhemoglobin (oxy-Hb) concentration in the left rostral prefrontal cortex in the child abuse group compared to the no-abuse group during the Wisconsin Card Sorting Test (WCST). A similar, albeit non-significant, trend toward decreased oxy-Hb concentration was observed in the child abuse group in the right dorsolateral prefrontal cortex (dlPFC) on the OSPAN and Connors CPT. The results suggest that the latter group may show subtle neurological deficits that persist into adulthood that may not manifest on traditional measures of cognitive function. These findings have implications for the development of remediation and treatment strategies in this population.

Treatment outcomes widely vary for individuals diagnosed with major depressive disorder, implicating a need for deeper understanding of the biological mechanisms conferring a greater likelihood of response to a particular treatment. Our improved understanding of intrinsic brain networks underlying depression psychopathology via magnetic resonance imaging and other neuroimaging modalities has helped reveal novel and potentially clinically meaningful biological markers of response. And while we have made considerable progress in identifying such biomarkers over the last decade, particularly with larger, multisite trials, there are significant methodological and practical obstacles that need to be overcome to translate these markers into the clinic. The aim of this review is to review current literature on brain network structural and functional biomarkers of treatment response or selection in depression, with a specific focus on recent large, multisite trials reporting predictive accuracy of candidate biomarkers. Regarding pharmaco- and psychotherapy, we discuss candidate biomarkers, reporting that while we have identified candidate biomarkers of response to a single intervention, we need more trials that distinguish biomarkers between first-line treatments. Further, we discuss the ways prognostic neuroimaging may help to improve treatment outcomes to neuromodulation-based therapies, such as transcranial magnetic stimulation and deep brain stimulation. Lastly, we highlight obstacles and technical developments that may help to address the knowledge gaps in this area of research. Ultimately, integrating neuroimaging-derived biomarkers into clinical practice holds promise for enhancing treatment outcomes and advancing precision psychiatry strategies for depression management. By elucidating the neural predictors of treatment response and selection, we can move towards more individualized and effective depression interventions, ultimately improving patient outcomes and quality of life.

This study aimed to identify different symptom trajectories based on the severity of depression symptoms within a 2-month follow-up, and to explore predictive factors for different symptom trajectories. Three hundred and ninety-two adults diagnosed with major depressive disorder (MDD) were recruited from two longitudinal cohorts. Patients received antidepressant treatment as usual, and the depression symptoms were evaluated by the 17-item Hamilton depression rating scale (HAMD-17) at baseline, two weeks, and eight weeks. Based on the HAMD-17 scores, different trajectories of symptom change were distinguished by applying Growth Mixture Modeling (GMM). Furthermore, the baseline sociodemographic, clinical, and cognitive characteristics were compared to identify potential predictors for different trajectories. Through GMM, three unique depressive symptom trajectories of MDD patients were identified: (1) mild-severity class with significant improvement (Mild, n = 255); (2) high-severity class with significant improvement (High, n = 39); (3) moderate-severity class with limited improvement (Limited, n = 98). Among the three trajectories, the Mild class had a relatively low level of anxiety symptoms at baseline, whereas the High class had the lowest education level and the worst cognitive performance. Additionally, participants in the Limited class exhibited an early age of onset and experienced a higher level of emotional abuse. MDD patients could be categorised into three distinct latent subtypes through different symptom trajectories in this study, and the characteristics of these subtype patients may inform identifications for trajectory-specific intervention targets.

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders. By pooling images from various cohorts, statistical power has increased, enabling the detection of subtle abnormalities and robust associations, and fostering new research methods. Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment. Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies. We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders. However, challenges such as data harmonization across different sites, privacy protection, and effective data sharing must be addressed. With proper governance and open science practices, we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis, treatment selection, and outcome prediction, contributing to optimal brain health.

The objective of this study was to examine sex differences in the antidepressant and neurocognitive effects of adjunctive nonconvulsive electrotherapy (NET) in patients with treatment-refractory depression (TRD), which has not yet been thoroughly investigated.

The study enrolled 20 patients with TRD, comprising 11 males and 9 females, who underwent a series of 6 NET sessions. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depressive symptoms, response, and remission at baseline and after the first, third, and sixth NET sessions. The Wisconsin Card Sorting Test (WCST) was used to assess neurocognitive function at baseline and after the sixth NET session.

After completing 6 NET sessions, female patients experiencing TRD exhibited a higher inclination toward achieving an antidepressant response (77.8% vs. 45.5%, P  = .197) and antidepressant remission (22.2% vs. 0%, P  = .189) when compared to their male counterparts. No significant differences were observed in changes in the HAMD-17 and WCST subscale scores (all P > .05), including completing classification number, total error number, persistent error number, and random error number between males and females. Additionally, no significant correlations were observed between baseline WCST subscale scores and changes in HAMD-17 scores or endpoint scores, irrespective of sex (all P > .05).

These pilot findings suggest that female patients with TRD exhibited increased rates of achieving antidepressant response and remission after undergoing NET. However, further studies should be conducted to confirm these findings.

Whether remitted major depressive disorder (rMDD) and MDD present common or distinct neuropathological mechanisms remains unclear. We performed a meta-analysis of task-related whole-brain functional magnetic resonance imaging (fMRI) using anisotropic effect-size signed differential mapping software to compare brain activation between rMDD/MDD patients and healthy controls (HCs). We included 18 rMDD studies (458 patients and 476 HCs) and 120 MDD studies (3746 patients and 3863 HCs). The results showed that MDD and rMDD patients shared increased neural activation in the right temporal pole and right superior temporal gyrus. Several brain regions, including the right middle temporal gyrus, left inferior parietal, prefrontal cortex, left superior frontal gyrus and striatum, differed significantly between MDD and rMDD. Meta-regression analyses revealed that the percentage of females with MDD was positively associated with brain activity in the right lenticular nucleus/putamen. Our results provide valuable insights into the underlying neuropathology of brain dysfunction in MDD, developing more targeted and efficacious treatment and intervention strategies, and more importantly, providing potential neuroimaging targets for the early screening of MDD.

There are various types of traumatic stimuli, such as catastrophic events like wars, natural calamities like earthquakes, and personal trauma from physical and psychological neglect or abuse and sexual abuse. Traumatic events can be divided into type I and type II trauma, and their impacts on individuals depend not only on the severity and duration of the traumas but also on individuals' self-evaluation of the traumatic events. Individual stress reactions to trauma include posttraumatic stress disorder (PTSD), complex PTSD and trauma-related depression. Trauma-related depression is a reactive depression with unclear pathology, and depression occurring due to trauma in the childhood has gained increasing attention, because it has persisted for a long time and does not respond to conventional antidepressants but shows good or partial response to psychotherapy, which is similar to the pattern observed for PTSD. Because trauma-related depression is associated with high risk of suicide and is chronic with a propensity to relapse, it is necessary to explore its pathogenesis and therapeutic strategy.

Cognitive impairment is a core feature of mood disorders and has been identified as an important treatment target. A better understanding of the factors contributing to cognitive impairment in mood disorders would be beneficial in developing interventions to address cognitive impairment. One key factor is childhood trauma. The aim of this review was to systematically synthesise and review research examining associations between reported childhood trauma and cognitive functioning in mood disorders.

Studies in adult samples examining the relationship between objective cognitive function and reported childhood trauma in major depressive disorder and/or bipolar disorder (in-episode or euthymia) were identified. Searches were conducted on PubMed, Embase and PsycINFO until January 2022. A narrative review technique was used due to the heterogeneity of group comparisons, cognitive tests and data analysis across studies.

Seventeen studies met the criteria for inclusion (mood disorders N = 1723, healthy controls N = 797). Evidence for childhood trauma being related to poorer cognitive functioning was consistent across global cognitive functioning and executive function domains for euthymic patients and psychomotor speed for in-episode patients. There was mixed evidence for verbal learning and memory and executive function for in-episode patients. Identification of patterns within other domains was difficult due to limited number of studies.

Findings from this review suggest childhood trauma is associated with poorer cognitive functioning in people with mood disorders. Targeted interventions to improve cognition may be warranted for this group.

Adverse childhood experiences have been linked to increased multimorbidity, with physical and mental health consequences throughout life. Chronic pain is often associated with mood disorders, such as major depressive disorder (MDD); both have been linked to adverse childhood experiences. It is unclear how the effect of adverse childhood experiences on neural processing impacts on vulnerability to chronic pain, MDD, or both, and whether there are shared mechanisms. We aimed to assess evidence for central neural changes associated with adverse childhood experiences in subjects with chronic pain, MDD, or both using systematic review and meta-analysis.

Electronic databases were systematically searched for neuroimaging studies of adverse childhood experiences, with chronic pain, MDD, or both. Two independent reviewers screened title, abstracts, and full text, and assessed quality. After extraction of neuroimaging data, activation likelihood estimate meta-analysis was performed to identify significant brain regions associated with these comorbidities.

Forty-nine of 2414 studies were eligible, of which 43 investigated adverse childhood experiences and MDD and six investigated adverse childhood experiences and chronic pain. None investigated adverse childhood experiences, chronic pain, and MDD together. Functional and structural brain abnormalities were identified in the superior frontal, lingual gyrus, hippocampus, insula, putamen, superior temporal, inferior temporal gyrus, and anterior cerebellum in patients with MDD exposed to adverse childhood experiences. In addition, brain function abnormalities were identified for patients with MDD or chronic pain and exposure to adverse childhood experiences in the cingulate gyrus, inferior parietal lobule, and precuneus in task-based functional MRI studies.

We found that adverse childhood experiences exposure can result in different functional and structural brain alterations in adults with MDD or chronic pain compared with those without adverse childhood experiences.

PROSPERO CRD42021233989.

Major depressive disorder is among the most prevalent psychiatric disorders, exacting a substantial personal, social, and economic toll. Antidepressant treatment typically involves an individualized trial and error approach with an inconsistent success rate. Despite a pressing need, no reliable biomarkers for predicting treatment outcome have yet been discovered. Brain MRI measures hold promise in this regard, though clinical translation remains elusive. In this review, we summarize structural MRI and functional MRI (fMRI) measures that have been investigated as predictors of treatment outcome. We broadly divide these into five categories including three structural measures: volumetric, white matter burden, and white matter integrity; and two functional measures: resting state fMRI and task fMRI. Currently, larger hippocampal volume is the most widely replicated predictor of successful treatment. Lower white matter hyperintensity burden has shown robustness in late life depression. However, both have modest discriminative power. Higher fractional anisotropy of the cingulum bundle and frontal white matter, amygdala hypoactivation and anterior cingulate cortex hyperactivation in response to negative emotional stimuli, and hyperconnectivity within the default mode network (DMN) and between the DMN and executive control network also show promise as predictors of successful treatment. Such network-focused measures may ultimately provide a higher-dimensional measure of treatment response with closer ties to the underlying neurobiology.

Recent studies have examined the role that the serotonergic system plays in moderating the association between adverse childhood experiences (ACEs) and depressive and anxiety disorders in adulthood. The aim of this literature review is to synthesize studies that examined serotonin's impact in relation to ACEs, and depressive and anxiety disorders in this population.

Published studies from 2008 to 2018 were retrieved from PubMed, CINAHL, and PsychINFO databases, and were included if ACEs, the serotonergic system, and depressive and or anxiety disorders were assessed in those with a mean age between nineteen and forty.

Twenty-eight studies were included. Various genetic polymorphisms in the serotonergic signaling system moderated the association between ACEs and depression. Additionally, selective serotonin reuptake inhibitors with a high affinity for the serotonin transporter, resulted in poor treatment outcomes for those with history of ACEs.

Additional research is needed in order to further define the role that the serotonergic genes play in the association between ACEs and depressive and anxiety disorders in adulthood.

Working memory (WM) impairments are common features of psychiatric disorders. A systematic meta-analysis was performed to determine common and disorder-specific brain fMRI response during performance of WM tasks in patients with SZ and patients with MDD relative to healthy controls (HC). Thirty-four published fMRI studies of WM in patients with SZ and 18 published fMRI studies of WM in patients with MDD, including relevant HC, were included in the meta-analysis. In both SZ and MDD there was common stronger fMRI response in right medial prefrontal cortex (MPFC) and bilateral anterior cingulate cortex (ACC), which are part of the default mode network (DMN). The effects were of greater magnitude in SZ than MDD, especially in prefrontal-temporal-cingulate-striatal-cerebellar regions. In addition, a disorder-specific weaker fMRI response was observed in right middle frontal gyrus (MFG) in MDD, relative to HC. For both SZ and MDD a significant correlation was observed between the severity of clinical symptoms and lateralized fMRI response relative to HC. These findings indicate that there may be common and distinct anomalies in brain function underlying deficits in WM in SZ and MDD, which may serve as a potential functional neuroimaging-based diagnostic biomarker with value in supporting clinical diagnosis, measuring illness severity and assessing the efficacy of treatments for SZ and MDD at the brain level.

After participating in this activity, learners should be better able to:• Identify the effects of dysregulated opioid signalling in depression• Evaluate the use of opioid compounds and ketamine in patients with depression ABSTRACT: Major depressive disorder (MDD) remains one of the leading causes of disability and functional impairment worldwide. Current antidepressant therapeutics require weeks to months of treatment prior to the onset of clinical efficacy on depressed mood but remain ineffective in treating suicidal ideation and cognitive impairment. Moreover, 30%-40% of individuals fail to respond to currently available antidepressant medications. MDD is a heterogeneous disorder with an unknown etiology; novel strategies must be developed to treat MDD more effectively. Emerging evidence suggests that targeting one or more of the four opioid receptors-mu (MOR), kappa (KOR), delta (DOR), and the nociceptin/orphanin FQ receptor (NOP)-may yield effective therapeutics for stress-related psychiatric disorders. Furthermore, the effects of the rapidly acting antidepressant ketamine may involve opioid receptors. This review highlights dysregulated opioid signaling in depression, evaluates clinical trials with opioid compounds, and considers the role of opioid mechanisms in rapidly acting antidepressants.

Childhood abuse and neglect increase the risk for psychiatric disorders (e.g., depression and anxiety) during adulthood and have been associated with deficits in cognitive control. The specific mechanisms underlying these cognitive control deficits are still unknown.

This study examined the expectation for reward to improve inhibitory control in young women (ages 18-35 years) with a history of childhood sexual and/or physical abuse (AG, N = 28), childhood emotional and/or physical neglect (NG, N = 30), or unaffected comparison women (HC, N = 40). They completed a previously validated rewarded (color-word) Stroop task and filled out questionnaires on depression, anxiety, and resilience.

Surprisingly, a significant group by reward interaction revealed larger performance benefits under reward prospect (relative to no-reward) for the AG group relative to both the NG and HC groups.

A small sample size limiting generalizability.

These results demonstrate sensitivity of abused subjects to reward in modulating cognitive control and might aid in discussing whether using reward schedules during therapeutic interventions could be effective.

Depression is a leading cause of disability worldwide and improving its treatment is a core research priority for future programmes. A change in the view of psychological and biological processes, from seeing them as separate to complementing one another, has introduced new perspectives on pathological mechanisms of depression and treatment mode of action. This review presents a theoretical model that incorporated this novel approach, the cognitive neuropsychological hypothesis of antidepressant action. This model proposes that antidepressant treatments decrease the negative bias in the processing of emotionally salient information early in the course of antidepressant treatment, which leads to the clinically significant mood improvement later in treatment. The paper discusses the role of negative affective biases in the development of depression and response to antidepressant treatments. It also discusses whether the model can be applied to other antidepressant interventions and its potential translational value, including treatment choice, prediction of response and drug development.

Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.

Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM-, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM-, n = 80). Separate analyses in MDD participants who remitted were conducted.

DM+ had lower baseline global cognition, processing speed, and memory v. HM-, with no significant baseline differences amongst DM-, HM+, and HM- groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM-, scored significantly lower than HM- in working memory and processing speed.

Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.

Child abuse and other forms of adversity are associated with alterations in threat processing and emotion regulation brain circuits.

The goal of the current investigation is to determine if the availability of positive social support can ameliorate the negative impact of adversity on these brain systems.

Subjects included 55 children ages 7-16 (X = 11.8, SD = 2.0). Approximately one-third of the cohort had no significant history of adversity, one-third had a history of moderate adversity, and one-third had a history of severe adversity. Brain imaging was conducted at the University of Vermont using a 3.0 T Philips scanner.

The Emotional Go-NoGo task with fearful and calm facial stimuli was used to assess the neural correlates of threat processing and emotion regulation in children during functional magnetic resonance imaging (fMRI). Dimensional measures of anxiety, social supports, and children's adverse experiences were also obtained.

A conjunction analysis was used to test if trauma-related brain activation in responding to fearful vs. calm targets was impacted by social support. This approach identified multiple activation foci, including a cluster extending from the left amygdala to several other key brain regions involved in emotion regulation, including the orbitofrontal cortex, anterior cingulate cortex (ACC), anterior insula, nucleus accumbens, and frontal pole (Family Wise Error (FWE) correction, p < 0.05).

Greater social support may reduce the effect that adversity has on neural processing of threat stimuli, consistent with the protective role of positive supports in promoting resilience and recovery demonstrated in the literature.

This analysis investigates the efficacy of vortioxetine in adults with major depressive disorder (MDD) who report childhood or recent trauma.

Patient-level data were analyzed from 4 double-blind, randomized, placebo-controlled short-term studies investigating the efficacy of vortioxetine (5-20 mg/day) versus placebo in patients (18-75 years old) with DSM-IV-TR-defined MDD. Changes from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression - Improvement (CGI-I), and Sheehan Disability Scale (SDS) were examined at the individual study level and as in meta-analysis. A long-term relapse prevention study of 5 and 10 mg of vortioxetine was also analyzed. Traumatic events history was recorded at baseline.

Sixty-one percent of subjects (1113/1811) reported trauma history in the short-term studies. A significant effect vs. placebo was observed for vortioxetine on MADRS (10 mg, -2.2, P = .025; 20 mg, -4.4, P < .001), HAM-A (20 mg, -1.60, P = .012), CGI-I (5 mg, -0.3, P = .028; 10 mg, -0.3, P = .013; 20 mg, -0.50, P = .009), and SDS (20 mg, -2.3, P = .007) in patients with any trauma (childhood and/or recent). In the relapse prevention study, 51% (198/392) of subjects reported a history of trauma. Subjects with any trauma (childhood and/or recent) randomized to placebo were significantly more likely to relapse than subjects treated with vortioxetine (hazard ratio 2.8, P = .0019).

An exploratory analysis.

Vortioxetine showed significant short- and long-term efficacy on depressive and anxiety symptoms and overall functioning in this large subpopulation of MDD patients with a history of trauma. A significantly lower risk of relapse was also observed with vortioxetine.

The goal of treatment for depressive disorders is complete remission of depressive symptoms with full recovery of social function and prevention of recurrence. However, a large proportion of patients do not experience symptomatic remission after the initial treatment, with even lower rates of remission in the longer treatment term. The main objective of individualized treatment applied in psychiatry is to improve precision in disease diagnosis, prognosis, treatment choices, and treatment response. Diverse approaches and techniques, such as genomics, epigenomics, other omics, neural circuit, and artificial intelligence are related to precision psychiatry. Using biology and computational psychiatry tools to find potential biomarkers, and based on precision psychiatry, patients considered to belong to the same endophenotype will be possible to receive biomarkers-based treatment and better prognosis. Especially in the choice of intervention, individualized treatment should be considered. In this review, we present the development of precise treatment in depressive disorders and introduce advances in several domains toward precision medicine and individualized treatment. We pay particular attention to biomarkers and the development of new technologies in depressive disorders, which will help disease complete remission and functional recovery, seek better lives for patients suffered with depressive disorders.

Poor treatment response is a hallmark of major depressive disorder. To tackle this problem, recent neuroimaging studies have sought to characterize antidepressant response in terms of pretreatment differences in intrinsic functional brain networks. Our aim is to review recent studies that predict antidepressant response using intrinsic network connectivity. We discuss current methodological limitations and directions for future antidepressant biomarker studies.

Functional connectivity stemming from the subgenual and rostral anterior cingulate has shown particular consistency in predicting antidepressant response. Differences in this connectivity may prove fruitful in differentiating treatment responders to many antidepressant interventions. Future biomarker studies should integrate biological MDD subtypes to address the disorder's inherent clinical heterogeneity. These clinical and scientific advancements have the potential to address this population marked by limited treatment response. Methodological considerations, including patient selection, response criteria, and model overfitting, will require future investigation to ensure that biomarkers generalize for prospective prediction of treatment response.

Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample.

The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8-21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009-2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered.

Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p &lt; 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p &lt; 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition.

Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.

New antidepressants and individualized approaches to treatment, matching specific therapies to individual patients, are urgently needed. For this, a better understanding of processes underpinning the development of depressive symptoms and response to medications are required. The cognitive neuropsychological model offers a novel approach uniquely combining biological and psychological approaches to explain how antidepressants exert their effect, why there is a delay in the onset of their clinical effect, and how changes in emotional processing are an essential step for a clinical antidepressant effect to take place. The paper presents the model and its underpinnings in the form of research in both healthy and depressed individuals, as well as the potential for its practical use.

Previous research has shown cognitive dysfunction in adults with a history of child abuse. The purpose of the present study was to measure differences that exist in executive functioning skills between individuals who have been abused as children versus those without the history of childhood abuse.

The present study recruited 43 students from the University of North Dakota (33 women) between ages 18 and 23 years of age. The participants were administered several prescreening measures, including a measure of physical child abuse, emotional child abuse, and sexual child abuse. Based on responses to these measures, participants were grouped into a no-child-abuse group, a mild-child-abuse group, or a moderate-to-severe child abuse group. All participants were administered measures of executive functioning that included the Wisconsin Card Sorting Task, the Operation Span Task, and the Connors Continuous Performance Task with a simultaneous recording of electroencephalographic activity using a wireless 9 channel EEG system.

There was a statistically significant main effect of child abuse group (no child abuse vs. moderate-to-high child abuse) for the EEG-derived probability of cognitive workload during the OSPAN. Beta bandwidths for individuals in the drug abuse group, which served as a covariate, were also found to be significantly attenuated during the Connors CPT.

Individuals that have been abused as children must use significantly more mental effort to complete executive functioning tasks as compared to their non-abused counterparts. Increased neurological effort could be used to explain poor decision-making skills that are common within the population.

The failure of traditional antidepressant medications to adequately target cognitive impairment is associated with poor treatment response, increased risk of relapse, and greater lifetime disability. Opioid receptor antagonists are currently under development as novel therapeutics for major depressive disorder (MDD) and other stress-related illnesses. Although it is known that dysregulation of the endogenous opioid system is observed in patients diagnosed with MDD, the impact of opioidergic neurotransmission on cognitive impairment has not been systematically evaluated. Here we review the literature indicating that opioid manipulations can alter cognitive functions in humans. Furthermore, we detail the preclinical studies that demonstrate the ability of mu-opioid receptor and kappa-opioid receptor ligands to modulate several cognitive processes. Specifically, this review focuses on domains within higher order cognitive processing, including attention and executive functioning, which can differentiate cognitive processes influenced by motivational state.

This study assessed whether antidepressant drug treatment has a common effect on gray matter (GM) volume in MDD patients with and without childhood maltreatment (CM).

T1-weighted structural magnetic resonance imaging data were collected from 168 participants, including 51 MDD patients with CM, 31 MDD patients without CM, 48 normal controls with CM, and 38 normal controls without CM. MDD patients received 6 months of treatment with paroxetine, and 24 patients with CM, and 16 patients without CM received a second MRI scan. A whole-brain voxel-based morphometry approach was used to estimate GM volume in each participant at two time points. Two-way analysis of variance (ANOVA) was used to determine the effects of MDD and CM on GM volume at baseline. Repeated measures two-way ANOVA was used to determine the treatment-by-CM interactive effect and main effect of treatment during paroxetine treatment. We further investigated the relationship between GM volume and clinical variables.

At baseline, significant MDD-by-CM interactive effects on GM volume were mainly observed in the left parahippocampal gyrus, left entorhinal cortex, and left cuneus. GM volume was significantly lower mainly in the right middle temporal gyrus in patients with MDD than in normal controls. We did not find any significant treatment-by-CM interactive effects. However, a treatment-related increase in GM was found in the right middle temporal gyrus in both MDD groups.

These results suggest that paroxetine treatment operates via a shared neurobiological mechanism in MDD patients with and without CM.

Traumatic stressful events (TSEs) during childhood and adolescence are associated with increased risk for psychopathology and cognitive impairment. Aberrations in social cognition may contribute to the psychopathology risk. We examined performance differences on social cognitive measures between youths with high TSE exposure and no TSE exposure and how these effects vary in female and male individuals.

The Philadelphia Neurodevelopmental Cohort investigates clinical and cognitive phenotypes in a U.S. youth (aged 8-21 years) community population. Here we compared performance in social cognition tasks between youths with high exposure (≥3 TSEs, n = 830) and youths with no exposure (n = 5202). Three social cognition tasks were analyzed: 1) age differentiation, 2) emotion identification (happy, sad, angry, fearful, or neutral), and 3) emotion intensity differentiation (happy, sad, angry, and fearful).

A significant TSE group by sex interaction was observed in all social cognitive tasks. In the emotion identification task, male subjects with high traumatic stress exposure outperformed nonexposed male subjects; exposure did not affect performance in female subjects. In the emotion intensity differentiation task, female subjects with high traumatic stress exposure performed worse than nonexposed female subjects, with no difference in male subjects between exposure groups. Exploratory analyses revealed that sex differences were driven by improved identification of angry expressions in stress-exposed male subjects and poorer performance in differentiating intensity of happy expressions in stress-exposed female subjects.

Exposure to high levels of early life traumatic stress was associated with sex-specific differences in social cognition. These findings might be related to the sex-specific patterns of psychopathology emerging during adolescence.

Precision medicine is a new and important topic in psychiatry. Psychiatry has not yet benefited from the advanced diagnostic and therapeutic technologies that form an integral part of other clinical specialties. Thus, the vision of precision medicine as applied to psychiatry - 'precision psychiatry' - promises to be even more transformative than in other fields of medicine, which have already lessened the translational gap.

Herein, we describe 'precision psychiatry' and how its several implications promise to transform the psychiatric landscape. We pay particular attention to biomarkers and to how the development of new technologies now makes their discovery possible and timely. The adoption of the term 'precision psychiatry' will help propel the field, since the current term 'precision medicine', as applied to psychiatry, is impractical and does not appropriately distinguish the field. Naming the field 'precision psychiatry' will help establish a stronger, unique identity to what promises to be the most important area in psychiatry in years to come.

In summary, we provide a wide-angle lens overview of what this new field is, suggest how to propel the field forward, and provide a vision of the near future, with 'precision psychiatry' representing a paradigm shift that promises to change the landscape of how psychiatry is currently conceived.

Major depressive disorder (MDD) is severely disabling, and current treatments have limited efficacy. The glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine was recently repurposed as a rapidly acting antidepressant, catalysing the vigorous investigation of glutamate-signalling modulators as novel therapeutic agents for depressive disorders. In this Review, we discuss the progress made in the development of such modulators for the treatment of depression, and examine recent preclinical and translational studies that have investigated the mechanisms of action of glutamate-targeting antidepressants. Fundamental questions remain regarding the future prospects of this line of drug development, including questions concerning safety and tolerability, efficacy, dose-response relationships and therapeutic mechanisms.

Intact cognitive control or executive function has characteristic patterns in both behavior and functional neurocircuitry. Functional neuroimaging studies have shown that a frontal-cingulate-parietal-insular (i.e., "multiple demand") network forms a common functional substrate undergirding successful adaptation to diverse cognitive processing demands. Separate work on intact neurocognitive performance implicates a higher order factor that largely explains performance across domains and may reflect trait cognitive control capacity. In the current review we highlight findings from respective psychiatric disorders (i.e., psychotic, bipolar and unipolar depressive, anxiety, and substance use disorders) suggesting that cognitive control perturbations amidst psychopathology are most pronounced within these common brain and behavioral indices of adaptive cognitive functioning and moreover, are evident across disorders (i.e., transdiagnostically). Specifically, within each of the disorder classes impairments are consistent in the multiple demand network across a wide range of cognitive tasks. While severity varies between disorders, broad as opposed to domain-specific impairments consistently emerge in neurocognitive performance. Accumulating findings have revealed that phenotypically diverse psychiatric disorders share a common factor or vulnerability to dysfunction that is in turn related to broad neurocognitive deficits. Furthermore, we have observed that regions of the multiple demand network, which overlap with the salience network (dorsal anterior cingulate and bilateral anterior insula) are characterized by reduced gray matter transdiagnostically and predict weaker neurocognitive performance. In summary, transdiagnostic (as opposed to disorder-specific) patterns of symptomatic distress and neurocognitive performance deficits, concurrent with parallel anomalies of brain structure and function may largely contribute to the real-world socio-occupational impairment common across disorders.

Maltreatment is associated with chronic depression, high negative self-attributions, and lifetime psychopathology. Adolescence is a sensitive period for the formation of self-concept. Identifying neurobiomarkers of self-processing in depressed adolescents with and without maltreatment may parse the effects of trauma and depression on self-development and chronic psychopathology. Depressed adolescents (n = 86) maltreated due to omission (DO, n = 13) or commission (DCM, n = 28) or without maltreatment (DC, n = 45), and HCs (HC, n = 37) appraised positive and negative self-descriptors in the scanner. DCM and DO showed hypoactivity in the dorsal anterior cingulate cortex (dACC) while processing positive versus negative self-descriptors compared to DC youth, who in turn showed reduced dACC recruitment versus HC. HC youth showed the highest activation in the dACC and striatum during positive self-descriptors; these regions showed a linear decline in activity across DC, DO, and DCM. Low dACC activity to positive versus negative self-descriptors was linked to inadequate coregulation of children's emotions by parents. Negative self-cognitions prevalent in DCM and DO adolescents may be perpetuated by activity in the dACC and striatum. Reduced activation of the dACC and striatum for positive self-descriptors, coupled with enhanced activity for negative self-descriptors, may heighten the risk for persistent depression.

Posttraumatic stress disorder (PTSD) is characterized by conflicting findings of both increased and decreased amygdala and prefrontal reactivity to threat or trauma stimuli. Childhood maltreatment (CM), a potent risk factor for PTSD, exerts long-lasting influences on threat processing and prefrontal-amygdala function. This suggests that CM history may influence PTSD neural phenotypes related to threat processing. Here, we adapt a well-characterized emotional conflict paradigm to investigate CM effects on both emotional conflict and emotional valence processing within PTSD stratified by task relevance. Forty-two individuals with PTSD (22 reporting extensive CM history (PTSD-CM)) and 20 trauma-exposed healthy controls (TEHCs) underwent functional magnetic resonance imaging while identifying affect of emotional faces (fear and happy) overlaid with a goal-irrelevant emotional distractor word ("FEAR" or "HAPPY"). We examined effects of CM on conflict, conflict adaptation, valence-related activation (fear vs. happy) for goal-relevant (face) and goal-irrelevant stimuli (word), and valence effects in interaction with goal-relevancy (face vs. word). Though no activation differences between groups were observed for conflict contrasts nor for valence effects in the amygdala, CM status interacted with valence processing differences as a function of goal relevance in the left dorsolateral prefrontal cortex (dlPFC). Here, PTSD-CM displayed greater activation relative to PTSD to negative valence when stimuli were goal-irrelevant. CM history also moderated relationships between activation abnormalities and PTSD re-experiencing symptoms. These findings provide initial evidence that CM history augments dorsolateral prefrontal bias to implicitly processed stimulus valence in PTSD.