The Bulgarian Ministry of Health invited the European Psychiatric Association (EPA) to evaluate Bulgarian mental health care service provision in 2018. Bulgarian mental health services face very significant challenges including a legacy of historic underfunding, internal conflicts, poor planning, and the emigration of very high numbers of younger skilled staff that had followed accession to the European Union. There were significant disputes between stakeholders regarding the way forward and had been at least two unsuccessful previous external agency interventions that had attempted to find solutions.

This EPA position paper describes in detail the EPA mission to Bulgaria including methodology, findings, recommendations, and finally the positive actions and changes that are now underway as a result of the EPA report and intervention aimed at contributing towards improving Bulgarian mental health services.

After meetings with multiple stakeholders in the Bulgarian mental health system and analysis of data on service delivery, workforce, funding and configuration the EPA Panel agreed a list of twenty recommendations for change.

The EPA mission, with the collaboration of multiple stakeholders in Bulgaria, was successful in stimulating high level government action to improve mental health services. Despite longstanding differences, it was possible to involve the stakeholders in constructive dialogue. The importance of “speaking with one voice” was a key lesson learned.

Anorexia nervosa (AN) is a severe mental disorder. Body shape disturbances are key in the development and maintenance of AN. Only few data are available on inpatients with life-threatening AN. Therefore, we aimed to investigate if body shape difficulties—with a focus on both body checking and avoidance—could improve during hospitalization in both subtypes of AN and to ascertain eventual associations between body shape concerns upon admission and clinical outcome.

Upon hospital admission and end of treatment (EOT), 139 inpatients with AN completed Body Shape Questionnaire (BSQ), Body Checking Questionnaire (BCQ), and Body Image Avoidance Questionnaire (BIAQ) in addition to measures of eating and general psychopathology.

Patients with severe AN reported improved BSQ and BIAQ scores at EOT while BCQ did not significantly change. Diagnostic subtypes differed only in baseline BSQ scores and had an impact on the improvement in BSQ at EOT. Baseline BCQ was associated with patients’ clinical improvement at EOT, even after controlling for age, duration of illness, Body Mass Index, depression, and anxiety scores.

Data on body shape concerns and their trajectory during hospitalization for severe AN are lacking; our findings provide support to the effectiveness of hospitalization in improving body shape concerns and body avoidance, but not body checking. Also, baseline body shape concerns (especially body checking) impacted on clinical improvement. Future research is needed to identify treatments that could further improve the therapeutic approach to severe patients of AN in the acute setting.

Parental separation is a very common childhood adversity. The association between other adverse childhood experiences and an increased risk of psychosis has been reported. However, the evidence on the risk of psychosis for children of separated parents is limited. In this systematic review, cohort, case–control, and cross-sectional studies, comparing the risk of psychotic disorders for people with and without separated parents, were searched, critically appraised, and summarized.

Studies were searched in PubMed, EMBASE, PsycINFO, and the Web of Science, from database inception to September 2019. A meta-analysis, using random-effects models, was undertaken to obtain pooled estimates of the risk of psychosis among participants with separated parents.

Twelve studies, with 305,652 participants from 22 countries, were included in the review. A significantly increased risk of psychosis for those with separated parents was observed, with a pooled odds ratio: 1.53 (95% confidence interval [CI]: 1.29–1.76), p < 0.001. The association remained significant when cohort, case–control, and cross-sectional studies were analyzed separately. The five cohort studies included in this review showed and increased risk of psychosis with odds ratio: 1.47 (95% CI: 1.26–1.69), p < 0.001.

Parental separation is a common childhood adversity associated with an increased risk of psychosis. Although the risk for an individual child of separated parents is still low, given the high proportion of couple that separate, the increased rates of psychosis may be substantial in the population. Further studies on the risk of psychosis in those with separated parents, and the explanatory factors for this association, are required.

Stigma is one of the most important barriers to help-seeking and to personal recovery for people suffering from mental disorders. Stigmatizing attitudes are present among mental health professionals with negative effects on the quality of health care.

Network and moderator analysis were used to identify what path determines stigma, considering demographic and professional variables, personality traits, and burnout dimensions in a sample of mental health professionals (n = 318) from six Community Mental Health Services. The survey included the Attribution Questionnaire-9, the Maslach Burnout Inventory, and the Ten-Item Personality Inventory.

The personality trait of openness to new experiences resulted to determine lower levels of stigma. Burnout (personal accomplishment) interacted with emotional stability in predicting stigma, and specifically, for subjects with lower emotional stability lower levels of personal accomplishment were associated with higher levels of stigma.

Some personality traits may be accompanied by better empathic and communication skills, and may have a protective role against stigma. Moreover, burnout can increase stigma, in particular in subjects with specific personality traits. Assessing personality and burnout levels could help in identifying mental health professionals at higher risk of developing stigma. Future studies should determine whether targeted interventions in mental health professionals at risk of developing stigma may be effective in stigma prevention.

Studying offspring of schizophrenia (SZo) and bipolar disorder patients (BDo) provides important information on the putative neurodevelopmental trajectories underlying development toward severe mental illnesses. We compared intracranial volume (ICV), as a marker for neurodevelopment, and global and local brain measures between SZo or BDo and control offspring (Co) in relation to IQ and psychopathology.

T1-weighted magnetic resonance imaging (MRI) brain scans were obtained from 146 participants (8–19 years; 40 SZo, 66 BDo, 40 Co). Linear mixed models were applied to compare ICV, global, and local brain measures between groups. To investigate the effect of ICV, IQ (four subtests Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale-III) or presence of psychopathology these variables were each added to the model.

SZo and BDo had significantly lower IQ and more often met criteria for a lifetime psychiatric disorder than Co. ICV was significantly smaller in SZo than in BDo (d = −0.56) and Co (d = −0.59), which was largely independent of IQ (respectively, d = −0.54 and d = −0.35). After ICV correction, the cortex was significantly thinner in SZo than in BDo (d = −0.42) and Co (d = −0.75) and lateral ventricles were larger in BDo than in Co (d = 0.55). Correction for IQ or lifetime psychiatric diagnosis did not change these findings.

Despite sharing a lower IQ and a higher prevalence of psychiatric disorders, brain abnormalities in BDo appear less pronounced (but are not absent) than in SZo. Lower ICV in SZo implies that familial risk for schizophrenia has a stronger association with stunted early brain development than familial risk for bipolar disorder.

The implications of cannabis use in the onset of early psychosis and the severity of psychotic symptoms have resulted in a proliferation of studies on this issue. However, few have examined the effects of cannabis use on the cognitive symptoms of psychosis (i.e., neurocognitive functioning) in patients with first-episode psychosis (FEP). This systematic review and meta-analysis aim to assess the neurocognitive functioning of cannabis users (CU) and nonusers (NU) with FEP.

Of the 110 studies identified through the systematic review of 6 databases, 7 met the inclusion criteria, resulting in 14 independent samples and 78 effect sizes. The total sample included 304 CU with FEP and 369 NU with FEP. The moderator variables were age at first use, duration of use, percentage of males, and age.

Effect sizes were not significantly different from zero in any neurocognitive domain when users and NU were compared. Part of the variability in effect sizes was explained by the inclusion of the following moderator variables: (1) frequency of cannabis use (β = 0.013, F = 7.56, p = 0.017); (2) first-generation antipsychotics (β = 0.019, F = 34.46, p ≤ 0.001); and (3) country where the study was carried out (β = 0.266, t = 2.06, p = 0.043).

This meta-analysis indicates that cannabis use is not generally associated with neurocognitive functioning in patients with FEP. However, it highlights the deleterious effect of low doses of cannabis in some patients. It also stresses the importance of the type of antipsychotic prescription and cannabis dose as moderator variables in the neurocognitive functioning of CU with FEP.

Post-traumatic stress disorder (PTSD) is debilitating for patients and society. There are a number of treatment methods albeit not all patients respond to these and an interesting method using electroencephalography-based neurofeedback (EEG-NF) has become more prominent in recent years. This systematic review aimed to assess whether EEG-NF, compared with sham NF, other treatment, or no treatment, is effective for PTSD. Primary outcomes were self-harm, PTSD symptoms, level of functioning and health-related quality of life.

Systematic literature searches for randomized controlled trials (RCTs) were conducted in six databases. Random effects meta-analysis was performed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation.

Four RCTs were included (123 participants). Suicidal thoughts were significantly reduced after EEG-NF compared with a waiting list in a small study. PTSD symptoms were assessed in all studies with different instruments. Results were consistently in favor of EEG-NF with large effect sizes (standardized mean difference −2.30 (95% confidence interval: −4.37 to −0.24). One study reported significantly improved level of executive functioning and one study a reduction in use of psychotropic medication. Complications were scarcely reported. Certainty of evidence was assessed as very low for the four assessed outcomes.

Based on four RCTs, with several study limitations and imprecision, it is uncertain whether EEG-NF reduces suicidal thoughts, PTSD symptoms, medication use, or improves function. Although all studies showed promising results, further studies are needed to increase the certainty of evidence.

Borderline personality disorder (BPD) presents with symptoms across different domains, whose neurobiology is poorly understood.

We applied voxel-based morphometry on high-resolution magnetic resonance imaging scans of 19 female BPD patients and 50 matched female controls.

Group comparison showed bilateral orbitofrontal gray matter loss in patients, but no significant changes in the hippocampus. Voxel-wise correlation of gray matter with symptom severity scores from the Borderline Symptom List (BSL-95) showed overall negative correlation in bilateral prefrontal, right inferior temporal/fusiform and occipital cortices, and left thalamus. Significant (negative) correlations with BSL-95 subscores within the patient cohort linked autoaggression to left lateral prefrontal and insular cortices, right inferior temporal/temporal pole, and right orbital cortex; dysthymia/dysphoria to right orbitofrontal cortex; self-perception to left postcentral, bilateral inferior/middle temporal, right orbitofrontal, and occipital cortices. Schema therapy-based Young Schema Questionnaire (YSQ-S2) scores of early maladaptive schemas on emotional deprivation were linked to left medial temporal lobe gray matter reductions.

Our results confirm orbitofrontal structural deficits in BPD, while providing a framework and preliminary findings on identifying structural correlates of symptom dimensions in BPD, especially with dorsolateral and orbitofrontal cortices.

Operational definitions of mania are based on expert consensus rather than empirical data. The aim of this study is to identify the key domains of mania, as well as the relevance of the different signs and symptoms of this clinical construct.

A review of latent factor models studies in manic patients was performed. Before extraction, a harmonization of signs and symptoms of mania and depression was performed in order to reduce the variability between individual studies.

We identified 12 studies fulfilling the inclusion criteria and comprising 3039 subjects. Hyperactivity was the clinical item that most likely appeared in the first factor, usually covariating with other core features of mania, such as increased speech, thought disorder, and elevated mood. Depressive–anxious features and irritability–aggressive behavior constituted two other salient dimensions of mania. Altered sleep was frequently an isolated factor, while psychosis appeared related to grandiosity, lack of insight and poor judgment.

Our results confirm the multidimensional nature of mania. Hyperactivity, increased speech, and thought disorder appear as core features of the clinical construct. The mood experience could be heterogeneous, depending on the co-occurrence of euphoric (elevated mood) and dysphoric (irritability and depressive mood) emotions of varying intensity. Results are also discussed regarding their relationship with other constitutive elements of bipolar disorder, such as mixed and depressive states.

There is limited research on the interaction of both positive and negative daily-life environments with stress-related genetic variants on psychotic experiences (PEs) and negative affect (NA) across the extended psychosis phenotype. This study examined whether the FK506 binding protein 51 (FKBP5) variability moderates the association of positive and negative experiences in the moment with PEs and NA in participants with incipient psychosis and their nonclinical counterparts.

A total of 233 nonclinical and 86 incipient psychosis participants were prompted for a 1-week period to assess their day-to-day experiences. Participants were genotyped for four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080).

Multilevel analyses indicated that, unlike the risk haplotype, the protective FKBP5 haplotype moderated all the associations of positive experiences with diminished PEs and NA in incipient psychosis compared with nonclinical group.

Participants with incipient psychosis showed symptomatic improvement when reporting positive appraisals in the interpersonal domain, which suggests that these act as a powerful coping mechanism. The fact that this occurred in daily-life underscores the clinical significance of this finding and pinpoints the importance of identifying protective mechanisms. In addition, results seem to concur with the vantage sensitivity model of gene–environment interaction, which poses that certain genetic variants may enhance the likelihood of benefiting from positive exposures.

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.

Self-stigma is a major issue in serious mental illness (SMI) and is negatively associated with patient outcomes. Most studies have been conducted in schizophrenia (SZ). Less is known about self-stigma in other SMI and autism spectrum disorder (ASD). The objectives of this study are: (i) to assess the frequency of self-stigma in a multicentric nonselected psychiatric rehabilitation SMI and ASD sample; and (ii) to investigate the correlates of elevated self-stigma in different SMI conditions and in ASD.

A total of 738 SMI or ASD outpatients were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluations included sociodemographic data, illness characteristics, and standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, personal recovery, a large cognitive battery, and daily functioning assessment.

31.2% of the total sample had elevated self-stigma. The highest prevalence (43.8%) was found in borderline personality disorder and the lowest (22.2%) in ASD. In the multivariate analysis, elevated self-stigma was best predicted by early stages of personal recovery (moratorium, p = 0.001, OR = 4.0 [1.78–8.98]; awareness, p = 0.011, OR = 2.87 [1.28–6.44]), history of suicide attempt (p = 0.001, OR = 2.27 [1.37–3.76]), insight (p = 0.002, OR = 1.22 [1.08–1.38]), wellbeing (p = 0.037, OR = 0.77 [0.60–0.98]), and satisfaction with interpersonal relationships (p < 0.001, OR = 0.85 [0.78–0.93]).

The present study has confirmed the importance of addressing self-stigma in SMI and ASD patients enrolled in psychiatric rehabilitation. The effectiveness of psychiatric rehabilitation on self-stigma and the potential mediating effects of changes in self-stigma on treatment outcomes should be further investigated.

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.

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.

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.

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.

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.