Brain atrophy in anorexia nervosa (AN) is one of the most marked structural brain changes observed in mental disorders. In this study, we propose a whole brain analysis approach to characterize global and regional cerebral volumes in adolescents with restricting-type anorexia nervosa (AN-r).

A total of 48 adolescent females (age range 13–18 years) were enrolled in the study (24 right-handed AN-r in the early stages of the illness and treated in the same clinical setting and 24 age-matched healthy controls [HC]). High-resolution T1-weighted magnetic resonance images were acquired. Cerebral volumes, including the total amounts of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were obtained with the Statistical Parametric Mapping software (SPM8); specific cortical regional volumes were computed by applying an atlas-based cortical parcellation to the SPM8 GM segments. Analysis of variance (ANOVA) was performed to identify any significant between-group differences in global and regional brain volumes.

The analyses revealed reduced total GM volumes (p = 0.02) and increased CSF (p = 0.05) in AN-r, compared with HC. No significant between-group difference was found in WM volumes. At the regional level, significantly lower GM volumes in both frontal lobes (p = 0.006) and in the left insula (p = 0.016) were detected. No significant relationships were found between cerebral volumes and duration of illness, psychiatric comorbidities, psychopharmacological treatment, prepubertal phase, or presence of amenorrhea.

The topographic distribution of GM reduction in a homogenous group of AN-r involves regions responsible for the emotional and cognitive deficits associated with the illness. These findings are discussed in relation to the roles of the insular cortex and the frontal lobes.

Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.

The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).

Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.

Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

Schizophrenia is a leading cause of disability. People living with schizophrenia (PLWS) present unemployment, social isolation, excess mortality and morbidity, and poor quality of life. Early recognition and appropriate treatment reduce the risk of chronicity and comorbidity. Personalization and integration of pharmacological and psychosocial interventions, as well as accurate identification and management of psychiatric and somatic comorbidities, can significantly improve mental and physical health of PLWS, promoting recovery.

A three-step Delphi approach was used to explore consensus on the essential components of early recognition and intervention, personalization, and integration of care to improve schizophrenia outcome, and on barriers and challenges to close treatment gaps. The consensus involved 8 Italian experts of schizophrenia, 100 psychiatrists from academic and nonacademic settings, including representatives of Italian Society of Psychiatry, and 65 trainees in psychiatry.

A strong consensus (from mostly agree to totally agree) emerged on the importance of early diagnosis (97%), standardized assessments (91%), correct management of somatic and psychiatric comorbidities (99%), and personalization and integration of care (94%). Lack of time, human resources, and training were identified as the main barriers and challenges to the translation of knowledge into clinical practice.

The results of this Delphi study demonstrated a strong consensus on main components of schizophrenia care, as well as on unmet needs to promote best practice and gaps between knowledge and clinical practice. The involvement of a large group of professionals and trainees in this in-depth consensus process might contribute to raise awareness and stimulate innovative strategies to improve the outcome of PLWS.

Adults with attention deficit hyperactivity disorder (ADHD) frequently suffer from sleep problems and report high levels of daytime sleepiness compared to neurotypical controls, which has detrimental effect on quality of life.

We evaluated daytime sleepiness in adults with ADHD compared to neurotypical controls using an observer-rated sleepiness protocol during the Sustained Attention Response Task as well as electroencephalogram (EEG) slowing, a quantitative electroencephalographic measure collected during a short period of wakeful rest.

We found that adults with ADHD were significantly sleepier than neurotypical controls during the cognitive task and that this on-task sleepiness contributed to cognitive performance deficits usually attributed to symptoms of ADHD. EEG slowing predicted severity of ADHD symptoms and diagnostic status, and was also related to daytime sleepiness. Frontal EEG slowing as well as increased frontal delta were especially prominent in adults with ADHD. We have validated and adapted an objective observer-rated measure for assessing on-task sleepiness that will contribute to future sleep research in psychology and psychiatry.

These findings indicate that the cognitive performance deficits routinely attributed to ADHD and often conceptualized as cognitive endophenotypes of ADHD are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. Daytime sleepiness plays a major role in cognitive functioning of adults with ADHD.

To assess the prevalence of autism traits in individuals accessing gender affirming treatments, we conducted a cross-sectional survey in the regional specialist gender services in Northern Ireland.

One hundred and twenty-three individuals (38 adolescents and 69 adults) currently attending or who previously attended specialist gender services in Northern Ireland were recruited. Fifty-six individuals assigned male at birth (AMAB) and 66 individuals assigned female at birth (AFAB) took part in the study. Main outcome measures: Autism Quotient (AQ), Cambridge Behavior Scale (EQ), and RAADS-14.

Autism trait prevalence rates of 19.5% (AQ); 25.4% (RAADS-14); and 35.8% (poor empathy traits). A combined measure comprising all three provided a prevalence of 17.2%. There were no mean differences in the scores between AMAB (assigned male at birth) individuals and AFAB (assigned female at birth) individuals.

Autism traits present additional challenges during the assessment and treatment of individuals with gender dysphoria. Autism screening tools can aid in the identification of individual with additional needs.

General population data on associations between mental disorders and total mortality are rare. The aim was to analyze whether the number of mental disorders, single substance use, mood, anxiety, somatoform or eating disorders during the lifetime and whether treatment utilization may predict time to death 20 years later in the general adult population.

We used data from the Composite International Diagnostic Interview, which includes DSM-IV diagnoses for substance use, mood, anxiety, somatoform, and eating disorders, for a sample of 4,075 residents in Germany who were 18–64 years old in 1996. Twenty years later, mortality was ascertained using the public mortality database for 4,028 study participants. Cox proportional hazards models were applied for disorders that existed at any time in life before the interview.

The data revealed increased hazard ratios (HRs) for number of mental disorders (three or more; HR 1.4; 95% confidence interval [CI] 1.1–1.9) and for single disorders (alcohol dependence, dysthymia, panic disorder with agoraphobia, and hypochondriasis), with the reference group being study participants who had not suffered from any of the mental disorders analyzed and with adjustments made for age, sex, and education. Among individuals with any mental disorder during their lifetimes, having been an inpatient in treatment for a mental disorder was related to a higher HR (2.2; CI 1.6–3.0) than was not having been in any treatment for a mental disorder.

In this sample of adults in the general population, three or more mental disorders, alcohol dependence, dysthymia, panic disorder with agoraphobia, and hypochondriasis were related to premature death.

Aberrant emotional reactivity is a putative endophenotype for bipolar disorder (BD), but the findings of behavioral studies are often negative due to suboptimal sensitivity of the employed paradigms. This study aimed to investigate whether visual gaze patterns and facial displays of emotion during emotional film clips can reveal subtle behavioral abnormalities in remitted BD patients.

Thirty-eight BD patients in full or partial remission and 40 healthy controls viewed 7 emotional film clips. These included happy, sad, and neutral scenarios and scenarios involving winning, risk-taking, and thrill-seeking behavior of relevance to the BD phenotype. Eye gaze and facial expressions were recorded during the film clips, and participants rated their emotional reactions after each clip.

BD patients showed a negative bias in both facial displays of emotion and self-rated emotional responses. Specifically, patients exhibited more fearful facial expressions during all film clips. This was accompanied by less positive self-rated emotions during the winning and happy film clips, and more negative emotions during the risk-taking/thrill-related film clips.

These findings suggest that BD is associated with trait-related abnormalities in subtle behavioral displays of emotion processing. Future studies comparing patients with BD and unipolar depression are warranted to clarify whether these differences are specific to BD. If so, assessments of visual gaze and facial displays of emotion during emotional film clips may have the potential to be implemented in clinical assessments to aid diagnostic accuracy.

Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome. The aim of the current study was to test the ability of machine learning (ML) models applied to electronic medical records (EMRs) to predict ASD early in life, in a general population sample.

We used EMR data from a single Israeli Health Maintenance Organization, including EMR information for parents of 1,397 ASD children (ICD-9/10) and 94,741 non-ASD children born between January 1st, 1997 and December 31st, 2008. Routinely available parental sociodemographic information, parental medical histories, and prescribed medications data were used to generate features to train various ML algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross-validation by computing the area under the receiver operating characteristic curve (AUC; C-statistic), sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value [PPV]).

All ML models tested had similar performance. The average performance across all models had C-statistic of 0.709, sensitivity of 29.93%, specificity of 98.18%, accuracy of 95.62%, false positive rate of 1.81%, and PPV of 43.35% for predicting ASD in this dataset.

We conclude that ML algorithms combined with EMR capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.

A growing body of research suggests that deficient emotional self-regulation (DESR) is common and morbid among attention-deficit/hyperactivity disorder (ADHD) patients. The main aim of the present study was to assess whether high and low levels of DESR in adult ADHD patients can be operationalized and whether they are clinically useful.

A total of 441 newly referred 18- to 55-year-old adults of both sexes with Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5) ADHD completed self-reported rating scales. We operationalized DESR using items from the Barkley Current Behavior Scale. We used receiver operator characteristic (ROC) curves to identify the optimal cut-off on the Barkley Emotional Dysregulation (ED) Scale to categorize patients as having high- versus low-level DESR and compared demographic and clinical characteristics between the groups.

We averaged the optimal Barkley ED Scale cut-points from the ROC curve analyses across all subscales and categorized ADHD patients as having high- (N = 191) or low-level (N = 250) DESR (total Barkley ED Scale score ≥8 or <8, respectively). Those with high-level DESR had significantly more severe symptoms of ADHD, executive dysfunction, autistic traits, levels of psychopathology, and worse quality of life compared with those with low-level DESR. There were no major differences in outcomes among medicated and unmedicated patients.

High levels of DESR are common in adults with ADHD and when present represent a burdensome source of added morbidity and disability worthy of further clinical and scientific attention.

Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.

Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.

Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).

Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

We studied the cumulative incidence of physical illnesses, and the effect of early environmental factors (EEFs) on somatic comorbidity in schizophrenia, in nonschizophrenic psychosis and among nonpsychotic controls from birth up to the age of 50 years.

The sample included 10,933 members of the Northern Finland Birth Cohort 1966, of whom, 227 had schizophrenia and 205 had nonschizophrenic psychosis. Diagnoses concerning physical illnesses were based on nationwide registers followed up to the end of 2016 and classified into 13 illness categories. Maternal education and age, family type at birth and paternal socioeconomic status were studied as EEFs of somatic illnesses.

When adjusted by gender and education, individuals and especially women with nonschizophrenic psychosis had higher risk of morbidity in almost all somatic illness categories compared to controls, and in some categories, compared to individuals with schizophrenia. The statistically significant adjusted hazard ratios varied from 1.27 to 2.42 in nonschizophrenic psychosis. Regarding EEFs, single-parent family as the family type at birth was a risk factor for a higher somatic score among men with schizophrenia and women with nonschizophrenic psychosis. Maternal age over 35 years was associated with lower somatic score among women with nonschizophrenic psychosis.

Persons with nonschizophrenic psychoses have higher incidence of somatic diseases compared to people with schizophrenia and nonpsychotic controls, and this should be noted in clinical work. EEFs have mostly weak association with somatic comorbidity in our study.

Policies addressing the physical health of people with mental disorders have historically focused on those with severe mental illness (SMI), giving less prominence to the more prevalent common mental disorders (CMDs). Little is known about the comparative physical health outcomes of these patient groups. We aimed to first compare the: (a) number of past-year chronic physical conditions and (b) recent physical health service utilization between CMDs vs. SMI, and secondly compare these outcomes between people with CMDs vs. people without mental disorders.

We analyzed cross-sectional data from the third Adult Psychiatric Morbidity Survey, a representative sample of the English population. We determined the presence of physical conditions and health service utilization by self-report and performed logistic regression models to examine associations of these outcomes between participant groups.

Past-year physical conditions were reported by the majority of participants (CMDs, n = 815, 62.1%; SMI = 27, 63.1%) with no variation in the adjusted odds of at least one physical condition between diagnoses (odds ratio [OR] = 0.96, 95% confidence intervals [CI] 0.42–1.98, p = 0.784). People with CMDs were significantly more likely to be recently hospitalized relative to with those with SMI (OR = 6.33, 95% CI 5.50–9.01, p < 0.05). Having a CMD was associated with significantly higher odds of past-year physical conditions and recent health service utilization (all p < 0.001) compared with the general population.

People with CMDs experience excess physical health morbidities in a similar pattern to those found among people with SMI, while their somatic hospitalization rates are even more elevated. Findings highlight the importance of recalibrating existing public health strategies to bring equity to the physical health needs of this patient group.

Psychiatric disorders are a group of complex psychological syndromes with high prevalence. Recent studies observed associations between altered plasma proteins and psychiatric disorders. This study aims to systematically explore the potential genetic relationships between five major psychiatric disorders and more than 3,000 plasma proteins.

The genome-wide association study (GWAS) datasets of attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) were driven from the Psychiatric GWAS Consortium. The GWAS datasets of 3,283 human plasma proteins were derived from recently published study, including 3,301 study subjects. Linkage disequilibrium score (LDSC) regression analysis were conducted to evaluate the genetic correlations between psychiatric disorders and each of the 3,283 plasma proteins.

LDSC observed several genetic correlations between plasma proteins and psychiatric disorders, such as ADHD and lysosomal Pro-X carboxypeptidase (p value = 0.015), ASD and extracellular superoxide dismutase (Cu-Zn; p value = 0.023), BD and alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (p value = 0.007), MDD and trefoil factor 1 (p value = 0.011), and SCZ and insulin-like growth factor-binding protein 6 (p value = 0.011). Additionally, we detected four common plasma proteins showing correlation evidence with both BD and SCZ, such as tumor necrosis factor receptor superfamily member 1B (p value = 0.012 for BD, p value = 0.011 for SCZ).

This study provided an atlas of genetic correlations between psychiatric disorders and plasma proteome, providing novel clues for pathogenetic and biomarkers, therapeutic studies of psychiatric disorders.

The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression.

A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group.

In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4.

The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have emerged as important peripheral inflammatory biomarkers. Recent data suggest a possible role of the immune system in the pathophysiology of suicidal behavior (SB). The aim of this study is to evaluate the association among NLR, MLR, and PLR and SB in patients with major depressive disorder (MDD), and to test its validity as a biomarker for suicidality.

We evaluated 538 patients with MDD (mean age [standard deviation] = 43.87 [14.36] years; females: 68.8%). A logistic regression model was estimated to determine the independent factors associated with suicide risk in patients with and without a history of suicide attempt (SA).

Three hundred ninety-three patients (74.7%) had a personal history of SA. Patients with a previous SA were more frequently female (71.9% vs. 59.6%; p = 0.007), significantly younger (41.20 vs. 51.77 years; p < 0.001), had lower depression severity at enrolment (15.58 vs. 18.42; p < 0.000), and significantly higher mean NLR and PLR ratios (2.27 vs. 1.68, p = 0.001; 127.90 vs. 109.97, p = 0.007, respectively). In the final logistic regression model, after controlling for age, sex, and depression severity, NLR was significantly associated with SB (β = 0.489, p = 0.000; odds ratio [95% confidence intervals] = 1.631 [1.266–2.102]). We propose a cut-off value of NLR = 1.30 (sensitivity = 75% and specificity = 35%).

Our data suggest that NLR may be a valuable, reproducible, easily accessible, and cost-effective strategy to determine suicide risk in MDD.

The mechanisms linking cardiovascular disease (CVD) and depression are still not established. We investigated the impact of mental vulnerability on the relationship between CVD and depression.

A total of 19,856 individuals from five cohorts of random samples of the background population in Copenhagen were followed from baseline (1983–2011) until 2017 in Danish registries. Additive hazard and Cox proportional hazard models were used to analyze the effects of confounding by mental vulnerability as well as interactions between mental vulnerability and CVD on the risk of depression.

During follow-up, 15.3% developed CVD, while 18.1% experienced depression. A strong positive association between CVD and depression (hazard ratio: 3.60 [95% confidence intervals (CI): 3.30; 3.92]) corresponding to 35.4 (95% CI: 31.7; 39.1) additional cases per 1,000 person-years was only slightly attenuated after adjustment for mental vulnerability in addition to other confounders. Synergistic interaction between CVD and mental vulnerability was identified in the additive hazard model. Due to interaction between CVD and mental vulnerability, CVD was associated with 50.9 more cases of depression per 1,000 person-years among individuals with high mental vulnerability compared with individuals with low mental vulnerability.

Mental vulnerability did not explain the strong relationship between CVD and depression. CVD was associated with additional cases of depression among individuals with higher mental vulnerability indicating that this group holds the greatest potential for intervention, for example, in rehabilitation settings.

There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals.

The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped.

Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007).

ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.

Distinguishing prodromes of bipolar disorder (BD) specific to children/adolescents, adults, and elderly patients is essential. The primary objective of this systematic review was to determine initial and relapse prodromes identifying adult patients with BD.

PubMed, PsycINFO, and Web of Science databases were searched using a predetermined strategy. A controlled process of study selection and data extraction was performed.

The 22 articles selected included 1,809 adult patients with BD. Initial prodromes cited most frequently in these studies showed low specificity. Among relapse prodromes cited most frequently, more talkative than usual, increased energy/more goal-directed behavior, thoughts start to race, increased self-esteem, strong interest in sex, increase in activity, and spending too much were identified exclusively before a manic/hypomanic episode, while loss of interest and hypersomnia were detected only before a depressive episode. Initial prodromal phases lasted longer than prodromal relapse phases. In the selected studies, the most used prodrome identification procedure was the clinical interview.

For adult patients with BD, initial and relapse prodromes of manic, hypomanic, and depressive episodes were identified. It is proposed that the most frequent prodromes found in this review be incorporated into a smartphone app that monitors the functioning of people at risk of BD and patients who have already been diagnosed. Data from this app would constitute a relevant source of big data.