Serotonin-reuptake inhibitors (SRIs) are first-line pharmacotherapy for the treatment of body dysmorphic disorder (BDD), a common and severe disorder. However, prior research has not focused on or identified definitive predictors of SRI treatment outcomes. Leveraging precision medicine techniques such as machine learning can facilitate the prediction of treatment outcomes.

The study used 10-fold cross-validation support vector machine (SVM) learning models to predict three treatment outcomes (i.e. response, partial remission, and full remission) for 97 patients with BDD receiving up to 14-weeks of open-label treatment with the SRI escitalopram. SVM models used baseline clinical and demographic variables as predictors. Feature importance analyses complemented traditional SVM modeling to identify which variables most successfully predicted treatment response.

SVM models indicated acceptable classification performance for predicting treatment response with an area under the curve (AUC) of 0.77 (sensitivity = 0.77 and specificity = 0.63), partial remission with an AUC of 0.75 (sensitivity = 0.67 and specificity = 0.73), and full remission with an AUC of 0.79 (sensitivity = 0.70 and specificity = 0.79). Feature importance analyses supported constructs such as better quality of life and less severe depression, general psychopathology symptoms, and hopelessness as more predictive of better treatment outcome; demographic variables were least predictive.

The current study is the first to demonstrate that machine learning algorithms can successfully predict treatment outcomes for pharmacotherapy for BDD. Consistent with precision medicine initiatives in psychiatry, the current study provides a foundation for personalized pharmacotherapy strategies for patients with BDD.

Losing one's only child is a major traumatic life event that may lead to post-traumatic stress disorder (PTSD); however, the underlying mechanisms of its psychological consequences remain poorly understood. Here, we investigated subregional hippocampal functional connectivity (FC) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (NR3C1) in adults who had lost their only child.

A total of 144 Han Chinese adults who had lost their only child (51 adults with PTSD and 93 non-PTSD adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fMRI study (age: 40–67 years). FCs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [CA1], CA2, CA3, and dentate gyrus [DG]) and methylation levels of the NR3C1 gene were compared among the three groups.

Trauma-exposed adults, regardless of PTSD diagnosis, had weaker positive FC between the left hippocampal CA1, left DG, and the posterior cingulate cortex, and weaker negative FC between the right CA1, right DG, and several frontal gyri, relative to healthy controls. Compared to non-PTSD adults, PTSD adults showed decreased negative FC between the right CA1 region and the right middle/inferior frontal gyri (MFG/IFG), and decreased negative FC between the right DG and the right superior frontal gyrus and left MFG. Both trauma-exposed groups showed lower methylation levels of the NR3C1 gene.

Adults who had lost their only child may experience disrupted hippocampal network connectivity and NR3C1 methylation status, regardless of whether they have developed PTSD.

Family education programs (FEPs) target caregiving-related psychological distress for carers of relatives/friends diagnosed with serious mental health conditions. While FEPs are efficacious in reducing distress, the mechanisms are not fully known. Peer group support and greater mental health knowledge are proposed to reduce carers' psychological distress by reducing stigmatising attitudes and self-blame, and strengthening carers' relationship with their relative.

Adult carers (n = 1016) who participated in Wellways Australia's FEP from 2009 to 2016 completed self-report questionnaires at the core program's start and end, during the consolidation period, and at a 6-month follow-up. Those who enrolled early completed questionnaires prior to a wait-list period. We used linear mixed-effects modelling to assess the program's effectiveness using a naturalistic wait-list control longitudinal design, and multivariate latent growth modelling to test a theory-based process change model.

While there was no significant change over the wait-list period, psychological distress, self-blame and stigmatising attitudes significantly decreased, and communication and relationship quality/feelings increased from the core program's start to its end. Changes were maintained throughout the consolidation period and follow-up. Peer group support significantly predicted the declining trajectory of distress. Peer group support and greater knowledge significantly predicted declining levels of self-blame and stigmatising attitudes, and increasing levels of communication.

This is the first study to quantitatively validate the mechanisms underlying the effect of FEPs on carers' psychological distress. Peer group support is key in modifying carers' appraisals of their friend/relatives' condition. Continued implementation of FEPs within mental health service systems is warranted.

The cognitive model of depression suggests that cognitive therapy (CT) improves major depressive disorder (MDD) in part by changing depressive cognitive content (e.g. dysfunctional attitudes, hopelessness). The current analyses clarified: (1) the durability of improvements in cognitive content made by acute-phase CT responders; (2) whether continuation-phase CT (C-CT) or fluoxetine (FLX) further improves cognitive content; and (3) the extent to which cognitive content mediates continuation treatments’ effects on depressive symptoms and major depressive relapse/recurrence.

Out-patients with recurrent MDD who responded to acute-phase CT (n = 241) were randomized to 8 months of C-CT, FLX or pill placebo (PBO) and followed for an 24 additional months. Cognitive content was assessed approximately every 4 months using five standard patient-report measures.

Large improvements in cognitive content made during acute-phase CT were maintained for 32 months, with 78–90% of patients scoring in normal ranges, on average. Cognitive content varied little between C-CT, FLX and PBO arms, overall. Small, transient improvements in cognitive content in C-CT or FLX compared with PBO patients did not clearly mediate the treatments’ effects on depressive symptoms or on major depressive relapse/recurrence.

Outpatients with recurrent MDD who respond to acute-phase CT show durable improvements in cognitive content. C-CT or FLX may not continue to improve patient-reported cognitive content substantively, and thus may treat recurrent MDD by other paths.

Examining neurobiological mechanisms that may transmit the effects of childhood maltreatment on mental health in youth is crucial for understanding vulnerability to psychopathology. This study investigated associations between childhood maltreatment, adolescent structural brain development, and mental health trajectories into young-adulthood.

Structural magnetic resonance imaging data was acquired from 144 youth at three time points (age 12, 16, and 18 years). Childhood maltreatment was reported to occur prior to the first scan. Linear mixed models were utilized to examine the association between total childhood maltreatment, neglect, abuse and (i) amygdala and hippocampal volume development, and (ii) maturational coupling between amygdala/hippocampus volume and the thickness of prefrontal regions. We also examined whether brain development mediated the association between maltreatment and depressive and anxiety symptoms trajectories from age 12 to 28.

Total maltreatment, and neglect, were associated with positive maturational coupling between the amygdala and caudal anterior cingulate cortex (cACC), whereby at higher and lower levels of amygdala growth, maltreatment was associated with lower and higher PFC thinning, respectively. Neglect was also associated with maturational coupling of the hippocampus with prefrontal regions. While positive amygdala-cACC maturational coupling was associated with greater increases in anxiety symptoms, it did not significantly mediate the association between maltreatment and anxiety symptom trajectories.

We found maltreatment to be associated with altered patterns of coupling between subcortical and prefrontal regions during adolescence, suggesting that maltreatment is associated with the development of socio-emotional neural circuitry. The implications of these findings for mental health require further investigation.

Meta-analyses agree that depression is characterized by neurocognitive dysfunctions relative to nonclinical controls. These deficits allegedly stem from impairments in functionally corresponding brain areas. Increasingly, studies suggest that some performance deficits are in part caused by negative task-taking attitudes such as poor motivation or the presence of distracting symptoms. A pilot study confirmed that these factors mediate neurocognitive deficits in depression. The validity of these results is however questionable given they were based solely on self-report measures. The present study addresses this caveat by having examiners assess influences during a neurocognitive examination, which were concurrently tested for their predictive value on performance.

Thirty-three patients with depression and 36 healthy controls were assessed on a battery of neurocognitive tests. The examiner completed the Impact on Performance Scale, a questionnaire evaluating mediating influences that may impact performance.

On average, patients performed worse than controls at a large effect size. When the total score of the Impact on Performance Scale was accounted for by mediation analysis and analyses of covariance, group differences were reduced to a medium effect size. A total of 30% of patients showed impairments of at least one standard deviation below the mean.

This study confirms that neurocognitive impairment in depression is likely overestimated; future studies should consider fair test-taking conditions. We advise researchers to report percentages of patients showing performance deficits rather than relying solely on overall group differences. This prevents fostering the impression that the majority of patients exert deficits, when in fact deficits are only true for a subgroup.

Disordered eating behaviors (DEB) impact on health and wellbeing worldwide. This study aimed to examine sociodemographic trends in the prevalence of DEB over 20 years in the Australian general population.

Data were derived from five sequential cross-sectional surveys (1998, 2008, 2009, 2016 and 2017) with population-representative samples of adults and adolescents residing in South Australia (N = 15 075). DEBs investigated were objective binge eating (OBE), strict dieting/fasting, and purging. Sociodemographic data included gender, age, educational level, work and marital status, and residence.

OBE prevalence increased significantly. Strict dieting/fasting also increased from 1998 to 2008/9 but remained stable between 2008/9 and 2016/7. Purging prevalence did not change significantly over time. All survey years were associated with a significantly higher odds of OBE, and strict diet/fasting compared to 1998. Lower age, a higher Accessibility Remoteness Index of Australia (ARIA) score, higher body mass index (BMI), higher educational attainment, and not being in a married or de facto relationship were independently associated with greater adjusted odds for endorsing OBE. Younger age, female gender, and higher BMI were also independently associated with greater adjusted odds for endorsing strict dieting/fasting.

The increased prevalence of DEBs in various strata of Australian society has both public health and clinical implications. The results refute the stereotype that eating disorders (EDs) predominantly affect young women. They build impetus for future research on EDs among men and older individuals, with a view to developing tailored public health and clinical interventions for these populations.

Group-based trajectory modeling holds promise for the study of prognostic indicators in the mood disorders because the courses that the individuals with these disorders follow are so highly variable. However, trajectory analyses of major depressive disorder have so far not included some of the more robust predictors of mood disorder outcome, nor have they described interactions between these predictors.

A group of 186 individuals aged 15–20 years with past or current depressive symptoms, who had recently begun taking a serotonin reuptake inhibitors antidepressant, underwent extensive baseline evaluations and were then followed for up to 2 years. Trajectory analyses used weekly ratings of depressive symptoms and the resulting groups were compared by the risk factors of sex, psychiatric comorbidity, negative emotionality, and childhood adversity.

A three-group solution provided the best statistical fit to the 2-year symptom trajectory. Negative emotionality and childhood adversity, though correlated, independently predicted membership in higher-morbidity groups. Female sex and comorbidity with generalized anxiety disorder (GAD) were also significantly more likely in the trajectory groups with higher symptom levels. However, the presence of GAD, rather than female sex, was the most important determinant of group membership. Negative emotionality was predictive of group membership only among women.

Trajectory analyses indicated that week-to-week variations in depressive symptoms across individuals could best be condensed into low, remitting and persistent symptom patterns. Female sex, anxiety symptoms, negative emotionality and childhood adversity were each independently associated with trajectories of higher morbidity but negative emotionality may be prognostically important only among women.

Borderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents and emerging adults. Here, we examined the contribution of fronto-limbic effective connectivity (EC) to the longitudinal stability of emotion-related impulsivity, a key feature of BPD, in symptomatic adolescents and young adults.

We compared resting-state EC in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13–30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We examined the association of directed centrality metrics with initial levels and rates of change in emotion-related impulsivity symptoms over a one-year follow-up using latent growth curve models (LGCMs).

In controls, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS, respectively. In the BPD group, bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs indicated that emotion-related impulsivity was stable across a one-year follow-up in the BPD group. Further, higher EC of R CeN to other regions in controls was associated with stronger within-person decreases in emotion-related impulsivity.

Functional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents and young adults, BLA may predominate over CeN activity, while in controls the ability of CeN to influence BLA activity predicted more rapid reductions in emotion-related impulsivity.

Major depressive disorder (MDD) is the main cause of disability worldwide, its outcome is poor, and its underlying mechanisms deserve a better understanding. Recently, peripheral acetyl-l-carnitine (ALC) has been shown to be lower in patients with major depressive episodes (MDEs) than in controls. l-Carnitine is involved in mitochondrial function and ALC is its short-chain acetyl-ester. Our first aim was to compare the plasma levels of l-carnitine and ALC, and the l-carnitine/ALC ratio in patients with a current MDE and healthy controls (HCs). Our second aim was to assess their changes after antidepressant treatment.

l-Carnitine and ALC levels and the carnitine/ALC ratio were measured in 460 patients with an MDE in a context of MDD and in 893 HCs. Depressed patients were re-assessed after 3 and 6 months of antidepressant treatment for biology and clinical outcome.

As compared to HC, depressed patients had lower ALC levels (p < 0.00001), higher l-carnitine levels (p < 0.00001) and higher l-carnitine/ALC ratios (p < 0.00001). ALC levels increased [coefficient: 0.18; 95% confidence interval (CI) 0.12–0.24; p < 0.00001], and l-carnitine levels (coefficient: −0.58; 95% CI −0.75 to −0.41; p < 0.00001) and l-carnitine/ALC ratios (coefficient: −0.41; 95% CI −0.47 to −0.34; p < 0.00001), decreased after treatment. These parameters were completely restored after 6 months of antidepressant. Moreover, the baseline l-carnitine/ALC ratio predicted remission after 3 months of treatment (odds ratio = 1.14; 95% CI 1.03–1.27; p = 0.015).

Our data suggest a decreased mitochondrial metabolism of l-carnitine into ALC during MDE. This decreased mitochondrial metabolism is restored after a 6-month antidepressant treatment. Moreover, the magnitude of mitochondrial dysfunction may predict remission after 3 months of antidepressant treatment. New strategies targeting mitochondria should be explored to improve treatments of MDD.

Negative symptoms such as blunted facial expressivity are characteristic of schizophrenia. However, it is not well-understood if and what abnormalities are present in individuals at clinical high-risk (CHR) for psychosis.

This experimental study employed facial electromyography (left zygomaticus major and left corrugator supercilia) in a sample of CHR individuals (N = 34) and healthy controls (N = 32) to detect alterations in facial expressions in response to emotionally evocative film clips and to determine links with symptoms.

Findings revealed that the CHR group showed facial blunting manifested in reduced zygomatic activity in response to an excitement (but not amusement, fear, or sadness) film clip compared to controls. Reductions in zygomatic activity in the CHR group emerged in response to the emotionally evocative peak period of the excitement film clip. Lower zygomaticus activity during the excitement clip was related to anxiety while lower rates of change in zygomatic activity during the excitement video clip were related to higher psychosis risk conversion scores.

Together, these findings inform vulnerability/disease driving mechanisms and biomarker and treatment development.

Preliminary evidence shows that discordance in stress experience, expression, and physiology (EEP) in adolescents is linked to depression, suicidal ideation (SI), non-suicidal self-injury (NSSI), and brain functioning. This study employs person-centered analysis to probe the relationship between stress responses, psychopathology, and neural patterns in female adolescents who are oversampled for engagement in NSSI.

Adolescent females (N = 109, ages 12–17) underwent a social stress test from which self-report measures of stress experience, observer ratings of stress expression, and physiological metrics of stress (via salivary cortisol) were obtained. Multi-trajectory modeling was employed to identify concordant and discordant stress EEP groups. Depressive symptoms, SI and attempt, NSSI engagement, frontal and limbic activation to emotional stimuli, and resting state fronto-limbic connectivity were examined in the EEP groups derived from the multi-trajectory models.

Four groups were identified, three of which demonstrated relatively concordant EEP and one which demonstrated discordant EEP (High Experience-High Expression-Low Physiology). Further, replicating past research, the High Experience-High Expression-Low Physiology discordant group exhibited higher depressive symptoms, SI, suicide attempt, and NSSI episodes (only for sensitivity analyses based on past year) relative to other EEP groups. No significant group differences in brain functioning emerged.

Results indicate that within-person, multi-level patterns in stress responding capture risk for dysfunction including depression and self-injurious thoughts and behaviors. Further interrogating of system-level stress functioning may better inform assessment and intervention efforts.

The diagnostic concept of unipolar mania (UM), i.e. the lifetime occurrence of mania without major depressive episodes, remains a topic of debate despite the evidence accumulated in the last few years. We carried out a systematic review and meta-analysis of observational studies testing factors associated with UM as compared to bipolar disorder with a manic-depressive course (md-BD).

Studies indexed up to July 2022 in main electronic databases were searched. Random-effects meta-analyses of the association between UM and relevant correlates yielded odds ratio (OR) or standardized mean difference (SMD), with 95% confidence intervals (CIs).

Based on data from 21 studies, factors positively or negatively associated with UM, as compared to md-BD, were: male gender (OR 1.47; 95% CI 1.11–1.94); age at onset (SMD −0.25; 95% CI −0.46 to −0.04); number of hospitalizations (SMD 0.53; 95% CI 0.21–0.84); family history of depression (OR 0.55; 95% CI 0.36–0.85); suicide attempts (OR 0.25; 95% CI 0.19–0.34); comorbid anxiety disorders (OR 0.35; 95% CI 0.26–0.49); psychotic features (OR 2.16; 95% CI 1.55–3.00); hyperthymic temperament (OR 1.99; 95% CI 1.17–3.40). The quality of evidence for the association with previous suicide attempts was high, moderate for anxiety disorders and psychotic features, and low or very low for other correlates.

Despite the heterogeneous quality of evidence, this work supports the hypothesis that UM might represent a distinctive diagnostic construct, with peculiar clinical correlates. Additional research is needed to better differentiate UM in the context of affective disorders, favouring personalized care approaches.