The factors associated with suicide attempts in major depressive disorder (MDD) patients with comorbid glucose disturbances remain unclear. To the best of our knowledge, this is the first study with a large sample size to examine risk factors of suicide attempts in first-episode drug-naïve (FEDN) MDD patients with comorbid glucose disturbances, including clinically relevant factors, metabolic parameters, and thyroid hormone levels. A total of 1718 FEDN MDD patients were enrolled. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess the clinical symptoms of patients. Fasting blood glucose, metabolic parameters, and thyroid hormone levels were measured. After controlling for HAMA and HAMD scores, the suicide attempt rate was 1.88 times higher in MDD patients with glucose disturbances than in MDD patients without glucose disturbances. Compared to non-suicide attempters, suicide attempters among the MDD patients with glucose disturbances had higher scores on HAMD and HAMA, PANSS positive symptoms, as well as higher levels of systolic and diastolic blood pressure, TC, LDL-C, thyroid stimulating hormone (TSH), TgAb, and thyroid peroxidases antibody (TPOAb). The combination of positive symptom score, HDL-C, systolic blood pressure, and marital status distinguished suicide attempters from non-suicide attempters. In addition, HAMA score, HAMD score, and TPOAb were associated with the number of suicide attempts in MDD patients with comorbid glucose disturbances. Our results suggest a high incidence of suicide attempts in MDD patients with comorbid glucose disturbances. Several clinically relevant factors, metabolic parameters, and thyroid hormone function have an impact on suicide attempts in MDD patients with comorbid glucose disturbances.
Recent findings have associated different COMT genotypes with working memory capacity in patients with fibromyalgia. Although it is thought that the COMT gene may influence neural correlates (P2 and P3 ERP components) underlying working memory impairment in this chronic-pain syndrome, it has not yet been explored. Therefore, the aim of the present research was to investigate the potential effect of the COMT gene in fibromyalgia patients on ERP working memory indices (P2 and P3 components). For this purpose, 102 participants (51 patients and 51 healthy control participants) took part in the experiment. Event-related potentials and behavioral responses were recorded while participants performed a spatial n-back task. Participants had to decide if the stimulus coincided or not in the same location as the one presented one (1-back condition) or two (2-back condition) trials before. Genotypes of the COMT gene were determined through a saliva sample from all participants. Present results significantly showed lower working memory performance ( p < 0.05) in patients with fibromyalgia as compared to control participants (higher rate of errors and slower reaction times). At neural level, we found that patients exhibited enhanced frontocentral and parieto-occipital P2 amplitudes compared to control participants ( p < 0.05). Interestingly, we also observed that only fibromyalgia patients carrying the Val/Val genotype of the COMT gene showed higher frontocentral P2 amplitudes than control participants ( p < 0.05). Current results (behavioral outcomes and P2 amplitudes) confirmed the presence of an alteration in working memory functioning in fibromyalgia. The enhancement of frontocentral P2 could be reflecting that these patients would manifest an inefficient way of activating executive attention processes, in carriers of the Val/Val genotype of COMT. To our knowledge, the present findings are the first linking neural indices of working memory dysfunctions and COMT genotypes in fibromyalgia. Applying a subgroup of patient’s strategy based on this genetic marker could be useful to establish more tailored therapeutical approaches.
Insomnia disorder (ID) and obstructive sleep apnea (OSA) are the two most prevalent sleep disorders worldwide, but the pathological mechanism has not been fully understood. Functional neuroimaging findings indicated regional abnormal neural activities existed in both diseases, but the results were inconsistent. This meta-analysis aimed to explore concordant regional functional brain changes in ID and OSA, respectively. We conducted a coordinate-based meta-analysis (CBMA) of resting-state functional magnetic resonance imaging (rs-fMRI) studies using the anisotropic effect-size seed‐based d mapping (AES-SDM) approach. Studies that applied regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) or fractional ALFF (fALFF) to analyze regional spontaneous brain activities in ID or OSA were included. Meta-regressions were then applied to investigate potential associations between demographic variables and regional neural activity alterations. Significantly increased brain activities in the left superior temporal gyrus (STG.L) and right superior longitudinal fasciculus (SLF.R), as well as decreased brain activities in several right cerebral hemisphere areas were identified in ID patients. As for OSA patients, more distinct and complicated functional activation alterations were identified. Several neuroimaging alterations were functionally correlated with mean age, duration or illness severity in two patients groups revealed by meta-regressions. These functionally altered areas could be served as potential targets for non-invasive brain stimulation methods. This present meta-analysis distinguished distinct brain function changes in ID and OSA, improving our knowledge of the neuropathological mechanism of these two most common sleep disturbances, and also provided potential orientations for future clinical applications.
Registration number: CRD42022301938.
Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the implication of this neurotransmitter in ASB is unclear. Here, we performed the first-ever postmortem analysis of serotonergic markers in the orbitofrontal cortex (OFC) of male subjects with ASB (n = 9). We focused on this brain region, given its well-recognized role in social response and ASB pathophysiology. Given that all individuals also had a substance use disorder (SUD) diagnosis, two age-matched control groups were used: SUD only and unaffected controls. Tissues were processed for immunoblotting analyses on eight key serotonergic targets: tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of brain serotonin synthesis; serotonin transporter (SERT), the primary carrier for serotonin uptake; monoamine oxidase A (MAOA), the primary enzyme for serotonin catabolism; and five serotonin receptors previously shown to influence social behavior: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4. Our analyses documented a significant increase in 5-HT2A receptor levels in the ASB + SUD group compared to SUD-only controls. Furthermore, TPH2 levels were significantly reduced in the SUD group (including SUD only and ASB + SUD) compared to unaffected controls. No difference was detected in the expression of any other serotonergic target. These results are in keeping with previous evidence showing high 5-HT2A receptor binding in the OFC of pathologically aggressive individuals and point to this molecule as a potential target for ASB treatment.
Poor knowledge about mental health disorders and their treatment likely contributes to the large treatment gap reported for mental health problems. Therefore, we studied the association between mental health literacy (MHL) and active help-seeking in a community sample. Participants were recruited from an add-on questionnaire study to the ‘Bern Epidemiological At-Risk’ (BEAR) study on 16–40-year-old community subjects of the Swiss canton Bern. At baseline, data of N = 1504, and at 3-year follow-up, data of N = 535 were available. Based on an unlabelled case vignette (on depression or schizophrenia), MHL was assessed by the questionnaire of Angermeyer and colleagues. Cross-sectional and longitudinal baseline predictors of help-seeking were analysed using path analyses. Additionally, sensitivity analyses of the prospective model were computed for sex, vignette, and baseline mental health problems/disorders. Cross-sectionally, help-seeking was associated with non-endorsement of biogenetic causal explanations, presence of mental health problems/disorders, help-seeking before baseline, poorer functioning, and lower health satisfaction. The prospective model was similar; yet, help-seeking at follow-up was associated with endorsements of the causal explanation ‘biogenetics’ and, additionally, ‘childhood trauma’ but not the presence of baseline mental health problems/disorders. Sensitivity analyses revealed a significant impact on sex, vignette, and mental health problems/disorders. For example, actual functional problems were predictive in males, while health satisfaction was predictive in females. Our findings indicate that future studies on drivers of help-seeking should assess very large community samples with case vignettes on different mental disorders to examine appropriate subgroups and their likely interaction to address group-specific factors in awareness campaigns.
Many individuals with major depression disorder (MDD) who achieve remission of depressive symptoms, do not perceive themselves as fully recovered. This study explores whether clinical remission is related to functional remission and to patient’s perception of recovery, as well as, which factors are associated with their functional and subjective remission. 148 patients with MDD in partial clinical remission were included. Demographics and clinical variables were collected through semi-structured interviews. Objective cognition was evaluated through a neuropsychological battery and subjective cognition through a specific questionnaire. The patient’s psychosocial functioning and the perception of their remission were also assessed. Apart from descriptive analysis, Pearson correlations and backward stepwise regression models explored the relationship between demographic, clinical, and cognitive factors with patients’ functional and self-perceived remission. From the whole sample, 57 patients (38.5%) were considered to achieve full clinical remission, 38 patients (25.7%) showed functional remission, and 55 patients (37.2%) perceived themselves as remitted. Depressive symptoms and objective and subjective executive function were the factors associated with psychosocial functioning. Besides, depressive symptoms, objective and subjective attention, and subjective executive function were the significant explanatory variables for self-perception of remission. The concept of full recovery from an episode of MDD should not only include the clinician’s perspective but also the patient’s psychosocial functioning along with their self-perceived remission. As residual depressive symptoms and cognition (objective and subjective) are factors with great contribution to a full recovery, clinicians should specifically address them when choosing therapeutic strategies.
Psychiatric patients are prone to mental health deterioration during the Covid-19 pandemic. Little is known about suicidality in psychiatric patients during the Covid-19 pandemic. This study is a retrospective chart review of psychiatric emergency department (pED) presentations with present or absent suicidality (5634 pED attendances, 4110 patients) in an academic pED in Berlin, Germany. Poisson regression analysis was performed on the effect of Covid-19 period on suicidality (suicidal ideation (SI), suicide plans (SP) or suicide attempt (SA)) during the first (3/2/2020–5/24/2020 “first-wave”) and second (9/15/2020–3/1/2021 “second-wave”) wave of the Covid-19 pandemic compared to the same periods one year earlier. During the first-wave the number of pED visits per person with SI, SP and SA was higher compared to one year earlier (SI RR = 1.614; p = 0.016; SP RR = 2.900; p = 0.004; SA RR = 9.862; p = 0.003). SI and SP were predicted by interaction between substance use disorder (SUD) and second-wave (SI RR = 1.305, p = 0.043; SP RR = 1.645, p = 0.018), SA was predicted by interaction between borderline personality disorder (BPD) and second-wave (RR = 7.128; p = 0.012). Suicidality increased during the first-wave of Covid-19 pandemic in our sample. In the second-wave this was found in patients with SUD and BPD. These patients may be at particular risk of suicidality during the Covid-19 pandemic.
As assessed by numerous neuropsychological tasks, individuals with autism spectrum disorder (ASD) and schizophrenia spectrum disorders (SSDs) have similar impairments related to executive functions (EFs). The neuropsychological profile of these two conditions was examined using the three-component EFs’ framework of Miyake and Friedman (Cogn Psychol 41(1):49-100, 2000). This approach assesses Inhibition (suppression of unwanted and irrelevant information/responses), Updating (use and control of contents of working memory), and Shifting (disengagement between activities or mental tasks) using nine different tasks. In line with previous research, we expected greater performance deficits in ASD in all three components compared to SSD, as well as faster responses for the SSD group. A self-paced task format allowed us to examine whether unlimited time given for a task would lead to better performance. The sample was constituted by the control group (N = 25), ASD group (N = 24), and SSD group (N = 12). Groups did not differ on Inhibition performance. In Updating, individuals with SSD performed poorer than the other groups. As for Shifting, both groups demonstrated poorer performance compared to controls, with the SSD group presenting the greatest difficulties. In terms of reaction time (RT), SSD participants’ RT were the slowest on Inhibition and Shifting tasks. There was a positive correlation between performance and time spent on Inhibition and Shifting only for the SSD group, which demonstrates that their performance improves when there are no time constraints. Our work provides a better understanding of spared and impaired EFs, which could be useful for designing strategies aimed at improving specific EFs in each group.
Previous research suggests a broad range of deficits in major depressive disorder. Our goal was to update the current assumptions and investigate the extent of cognitive impairment in depression in the acute and remitted state. A systematic review of the existing literature between 2009 and 2019 assessing the risk of bias within the included studies was performed. Of the 42 articles reviewed, an unclear risk of bias was shown overall. The risk of bias mainly concerned the sample selection, inadequate remedial measures, as well as the lack of blinding the assessors. In the acute phase, we found strong support for impairment in processing speed, learning, and memory. Follow-up studies and direct comparisons revealed less pronounced deficits in remission, however, deficits were still present in attention, learning and memory, and working memory. A positive correlation between the number of episodes and cognitive deficits as well as depression severity and cognitive deficits was reported. The results also demonstrate a resemblance between the cognitive profiles in bipolar disorder and depression. Comparisons of depression with schizophrenia led to unclear results, at times suggesting an overlap in cognitive performance. The main findings support the global deficit hypothesis and align with results from prior meta-analyses and reviews. Recommendations for future research are also presented.
Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear.
In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups.
In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score.
We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning.
The hypothesis of the psychosis continuum enables to study the mechanisms of psychosis risk not only in clinical samples but in non-clinical as well. The aim of this longitudinal study was to investigate self-disturbances (SD), a risk factor that has attracted substantial interest over the last two decades, in combination with trauma, cognitive biases and personality, and to test whether SD are associated with subclinical positive symptoms (PS) over a 12-month follow-up period. Our study was conducted in a non-clinical sample of 139 Polish young adults (81 females, age M = 25.32, SD = 4.51) who were selected for frequent experience of subclinical PS. Participants completed self-report questionnaires for the evaluation of SD (IPASE), trauma (CECA.Q), cognitive biases (DACOBS) and personality (TCI), and were interviewed for subclinical PS (CAARMS). SD and subclinical PS were re-assessed 12 months after baseline measurement. The hypothesized model for psychosis risk was tested using path analysis. The change in SD and subclinical PS over the 12-month period was investigated with non-parametric equivalent of dependent sample t-tests. The models with self-transcendence (ST) and harm avoidance (HA) as personality variables were found to be well-fitted and explained 34% of the variance in subclinical PS at follow-up. Moreover, we found a significant reduction of SD and subclinical PS after 12 months. Our study suggests that combining trauma, cognitive biases, SD and personality traits such as ST and HA into one model can enhance our understanding of appearance as well as maintenance of subclinical PS.
Advanced parental age at delivery and neurological soft signs (NSS) constitute risk factors for schizophrenia. The aim of the current study was to develop a neurobiological diagnostic index by combining them, and without the contribution of clinical symptomatology. The study sample included 133 patients suffering from schizophrenia according to DSM-IV-TR (77 males and 56 females; aged 33.55 ± 11.22 years old) and 122 normal controls (66 males and 56 females; aged 32.89 ± 9.91 years old). The assessment included the Neurological Evaluation Scale (NES), and a number of scales assessing the clinical symptoms and adverse effects. The statistical analysis included exploratory t-test, Pearson Correlation coefficient (R) and Discriminant Function Analysis (DFA). Exploratory t-tests and Pearson’s R suggested that sex, parental age and NSS constitute independent components. On the basis of DFA results, the Psychotic Neurological Index was developed. At the cut-off PNI score of 8.5, sensitivity was equal to 94.74 and specificity to 93.44. The current is probably the first study to report on an easily obtainable diagnostic neurobiological marker with identifiable properties which is absolutely independent from the clinical manifestations and could serve in distinguishing between patients with schizophrenia and healthy controls with high efficacy.
The rapidly evolving field of sensorimotor neuroscience reflects the scientific and clinical relevance of sensorimotor abnormalities as an intrinsic component of the disease process, e.g., in patients with schizophrenia spectrum disorders (SSD). Despite previous efforts, however, prevalence rates and relationships between different categories of sensorimotor abnormalities in SSD patients are still subject of ongoing debate. In this study, we examined five different categories of the sensorimotor domain (Neurological soft signs (NSS), parkinsonism, catatonia, akathisia, and tardive dyskinesia) according to well-established clinical ratings scales and the respective cut-off criteria in a sample of 131 SSD patients. We used a collection of statistical methods to better understand prevalence, overlap and heterogeneity, as well as psychopathological and cognitive correlates of sensorimotor abnormalities. 97.7% of the SSD patients considered by this study exhibited at least one categorically defined sensorimotor abnormality that tended to co-vary within three different sensorimotor subgroups (moderate, hyperkinetic and hypokinetic). Finally, hyperkinetic and hypokinetic groups differed significantly in their neurocognitive performance compared with the moderate group. The results suggest different patterns of clinical overlap, highlight the relationship between sensorimotor and cognitive domain and provide clues for further neurobiological studies.
Neuroimaging, genetic and molecular biological studies have shown impaired intra-cortical myelination in patients with schizophrenia, particularly in the prefrontal cortex. Previously we reported a significant deficit of oligodendrocytes and oligodendrocyte clusters in layers 3 and 5 of the prefrontal cortex, Brodmann area 10 (BA10) in schizophrenia. In this current study, we investigate the number of oligodendrocyte satellites (Sat-Ol) per pyramidal neuron in layer 5 of BA10 in schizophrenia (n = 17) as compared to healthy controls (n = 20) in the same section collection as previously used to study the numerical density (Nv) of oligodendrocytes and oligodendrocyte clusters. We find a significant reduction (− 39%, p < 0.001) in the number of Sat-Ol per neuron in schizophrenia as compared to the control group. The number of Sat-Ol per neuron did not correlate with the Nv of oligodendrocytes or with the Nv of oligodendrocyte clusters. Our previous studies of the inferior parietal lobule (BA39 and BA40), demonstrated significant decrease of the number of Sat-Ol only in patient subgroups with poor and fair insight. Additionally, correlation pattern between number of Sat-Ol and Nv of oligodendrocytes and oligodendrocyte clusters was similar between the two functionally interconnected cortical areas, BA10 and BA40, whereas in BA39, strong significant correlations were revealed between the number of Sat-Ol and Nv of oligodendrocyte clusters (0.9 ≤ R ≥ 0.66; p < 0.001). These data suggest that that specific features of Sat-Ol alterations patterns may be associated with specific activity-driven plasticity of corresponding networks in the brain of people with schizophrenia.
Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15–30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and follow-up, including follow-up levels of BSD (assessed with the EASE). Clinical high risk (CHR) for psychosis status and symptom severity were assessed with the SIPS/SOPS scales and also according to the cognitive basic symptoms high-risk criteria (COGDIS). DSM-IV diagnoses, functioning and other clinical characteristics were assessed with standard clinical instruments. Higher severity of negative symptoms and meeting COGDIS criteria at baseline were associated with higher BSD levels at follow-up. All measured at follow-up, higher BSD levels correlated with higher severity of positive, negative, disorganization and general symptoms, and with a lower level of global functioning. We found higher BSD levels at follow-up in subjects with schizotypal personality disorder (SPD) at baseline ( n = 5) and in SSDs at follow-up ( n = 12, including nine with SPD). Mean BSD levels decreased significantly from baseline to follow-up, but individual trajectories varied considerably. Increased BSD levels were associated with higher baseline BSD levels, non-remission of positive symptoms and functional decline. Overall, the current study indicates that subgroups in the CHR population with a higher risk of non-remission or deterioration may be identified by supplementing CHR criteria with assessment of BSD and negative symptoms.
Existing evidence suggests that emotion regulation is abnormal in schizophrenia and associated with undesirable clinical outcomes. However, this literature is based predominantly on trait self-report and does not indicate which stages of emotion regulation (identification, selection, implementation) are impaired. The current study focused on determining the nature of abnormalities at the identification stage using ecological momentary assessment (EMA). Participants included clinically stable outpatients with schizophrenia (SZ; n = 48) and healthy controls (CN; n = 52) who completed 6 days of EMA. The EMA surveys assessed emotional experience, emotion regulation, and symptoms. Results indicated that SZ identified the need to regulate at a higher rate than CN. Specifically, SZ displayed an inefficient threshold for identifying the need to regulate, such that they regulated too much when negative affect was low and too little when negative affect was high. Emotion regulation effort exertion was also inefficient, such that effort was too high at low levels of negative affect and too low at high levels of negative affect in SZ. These identification stage abnormalities also demonstrated differential associations with positive and negative symptoms. Findings suggest that identification stage abnormalities may create a bottleneck that feeds forward and impacts subsequent stages of emotion regulation in SZ that are critically related to symptoms. Targeting the psychological processes underlying these identification stage abnormalities might offer a novel means of treating positive and negative symptoms in schizophrenia.
In this first cross-sectional MRI study in acute catatonia, we compared the resting state whole-brain, within-network and seed (left precentral gyrus)-to-voxel connectivity, as well as cortical surface complexity between a sample of patients in acute retarded catatonic state (n = 15) diagnosed as per DSM-5 criteria and a demographically matched healthy control sample (n = 15). The patients had comorbid Axis-I psychiatric disorders including schizophrenia spectrum disorders and psychotic mood disorders, but did not have diagnosable neurological disorders. Acute retarded catatonia was characterized by reduced resting state functional connectivity, most robustly within the sensorimotor network; diffuse region of interest (ROI)-ROI hyperconnectivity; and seed-to-voxel hyperconnectivity in the frontoparietal and cerebellar regions. The seed (left precentral gyrus)-to-voxel connectivity was positively correlated to the catatonia motor ratings. The ROI–ROI as well as seed-to-voxel functional hyperconnectivity were noted to be higher in lorazepam responders (n = 9) in comparison to the non-responders (n = 6). The overall Hedges’ g effect sizes for these analyses ranged between 0.82 and 3.53, indicating robustness of these results, while the average Dice coefficients from jackknife reliability analyses ranged between 0.6 and 1, indicating fair (inter-regional ROI–ROI connectivity) to perfect (within-sensorimotor network connectivity) reliability of the results. The catatonia sample showed reduced vertex-wise cortical complexity in the right insular cortex and contiguous areas. Thus, we have identified neuroimaging markers of the acute retarded catatonic state that may show an association with treatment response to benzodiazepines. We discuss how these novel findings have important translational implications for understanding the pathophysiology of catatonia as well as for the mechanistic understanding and prediction of treatment response to benzodiazepines.
Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.
Hubs in the brain network are the regions with high centrality and are crucial in the network communication and information integration. Patients with schizophrenia (SCZ) exhibit wide range of abnormality in the hub regions and their connected functional connectivity (FC) at the whole-brain network level. Study of the hubs in the brain networks supporting complex social behavior (social brain network, SBN) would contribute to understand the social dysfunction in patients with SCZ. Forty-nine patients with SCZ and 27 healthy controls (HC) were recruited to undertake the resting-state magnetic resonance imaging scanning and completed a social network (SN) questionnaire. The resting-state SBN was constructed based on the automatic analysis results from the NeuroSynth. Our results showed that the left temporal lobe was the only hub of SBN, and its connected FCs strength was higher than the remaining FCs in both two groups. SCZ patients showed the lower association between the hub-connected FCs (compared to the FCs not connected to the hub regions) with the real-life SN characteristics. These results were replicated in another independent sample (30 SCZ and 28 HC). These preliminary findings suggested that the hub-connected FCs of SBN in SCZ patients exhibit the abnormality in predicting real-life SN characteristics.
This narrative review examines the possible role of microglial cells, first, in neuroinflammation and, second, in schizophrenia, depression, and suicide. Recent research on the interactions between microglia, astrocytes and neurons and their involvement in pathophysiological processes of neuropsychiatric disorders is presented. This review focuses on results from postmortem, positron emission tomography (PET) imaging studies, and animal models of schizophrenia and depression. Third, the effects of antipsychotic and antidepressant drug therapy, and of electroconvulsive therapy on microglial cells are explored and the upcoming development of therapeutic drugs targeting microglia is described. Finally, there is a discussion on the role of microglia in the evolutionary progression of human lineage. This view may contribute to a new understanding of neuropsychiatric disorders.
Episodic memory ability relies on hippocampal-prefrontal connectivity. However, few studies have examined relationships between memory performance and white matter (WM) microstructure in hippocampal-prefrontal pathways in schizophrenia-spectrum disorder (SSDs). Here, we investigated these relationships in individuals with first-episode psychosis (FEP) and chronic schizophrenia-spectrum disorders (SSDs) using tractography analysis designed to interrogate the microstructure of WM tracts in the hippocampal-prefrontal pathway. Measures of WM microstructure (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) were obtained for 47 individuals with chronic SSDs, 28 FEP individuals, 52 older healthy controls, and 27 younger healthy controls. Tractography analysis was performed between the hippocampus and three targets involved in hippocampal–prefrontal connectivity (thalamus, amygdala, nucleus accumbens). Measures of WM microstructure were then examined in relation to episodic memory performance separately across each group. Both those with FEP and chronic SSDs demonstrated impaired episodic memory performance. However, abnormal WM microstructure was only observed in individuals with chronic SSDs. Abnormal WM microstructure in the hippocampal-thalamic pathway in the right hemisphere was associated with poorer memory performance in individuals with chronic SSDs. These findings suggest that disruptions in WM microstructure in the hippocampal–prefrontal pathway may contribute to memory impairments in individuals with chronic SSDs but not FEP.
Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked distinct deviations of brain structure to illness insight, specifically in frontoparietal and subcortical regions. Some of these abnormalities are thought to reflect aberrant cortical development. In this study, we used cross-sectional data to examine associations between illness insight and two cortical surface markers that are known to follow distinct neurodevelopmental trajectories, i.e. cortical gyrification (CG) and thickness (CT). CG and CT was investigated in SZ patients (n = 82) and healthy controls (HC, n = 48) using 3 T structural magnetic resonance imaging. Illness insight in SZ patients was measured using the OSSTI scale, an instrument that provides information on two distinct dimensions of illness insight, i.e. treatment adherence (OSSTI-A) and identification of disease-related symptoms (OSSTI-I). CT and CG were computed using the Computational Anatomy Toolbox (CAT12). Whole-brain and regions-of-interest (ROI)-based analyses were performed. SZ patients showed higher CG in anterior cingulate, superior frontal and temporal gyrus and reduced CG in insular and superior frontal cortex when compared to HC. SZ patients showed decreased CT in pre- and paracentral, occipital, cingulate, frontoparietal and temporal regions. Illness insight in SZ patients was significantly associated with both CG and CT in the left inferior parietal lobule (OSSTI-A) and the right precentral gyrus (CG/OSSTI-A, CT/OSSTI-I). The data support a multi-parametric neuronal model with both pre- and postnatal brain developmental factors having an impact on illness insight in patients with SZ.
Difficulties in interpersonal communication, including conversational skill impairments, are core features of schizophrenia. However, very few studies have performed conversation analyses in a clinical population of schizophrenia patients. Here we investigate the conversational patterns of dialogues in schizophrenia patients to assess possible associations with symptom dimensions, subjective self-disturbances and social functioning. Thirty-five schizophrenia patients were administered the Positive and Negative Syndrome Scale (PANSS), the Clinical Language Disorder Rating Scale (CLANG), the Scale for the Assessment of Thought, Language and Communication (TLC), the Examination of Anomalous Self-Experience Scale (EASE), and the Social and Occupational Functioning Assessment Scale (SOFAS). Moreover, participants underwent a recorded semi-structured interview, to extract conversational variables. Conversational data were associated with negative symptoms and social functioning, but not with positive or disorganization symptoms. A significant positive correlation was found between “pause duration” and the EASE item “Spatialization of thought”. The present study suggests an association between conversational patterns and negative symptom dimension of schizophrenia. Moreover, our findings evoke a relationship between the natural fluidity of conversation and of the natural unraveling of thoughts.
Pathological gambling (PG) and methamphetamine-induced psychotic disorders (MIPD) both frequently occurs in methamphetamine-dependent individuals. The current study examined whether impulsivity mediated the relationship between MIPD and gambling severity. The sample consisted of 320 pathological gamblers with methamphetamine dependence (mean age 32.6 years, ranging from 15 to 64 years) voluntarily recruited from three rehabilitation centers in Hunan, China. The semistructured clinical interview of DSM-IV-TR Axis I Disorders Patient Edition was used to diagnosis the presence of MIPD and PG by registered psychiatrists. The severity of gambling symptoms was assessed using the global assessment of functioning scale, and the Barratt Impulsiveness Scale-11 provided a measure of impulsivity. Of the sample, 53.4% of participants (n = 171) met diagnostic criteria for MIPD. Individuals with a dual diagnosis of MIPD were associated with higher levels of impulsivity and greater gambling severity. Notably, support for our hypothesized mediation model was found such that impulsivity mediated the association between MIPD and gambling severity. Our findings imply that impulsivity appears to be a transdiagnostic process, which may be targeted in treatment among pathological gamblers with a dual diagnosis of MIPD to reduce gambling behaviors. Limits and future directions for research are discussed.
The self-concept—defined as the cognitive representation of beliefs about oneself—determines how individuals view themselves, others, and their actions. A negative self-concept can drive gaming use and internet gaming disorder (IGD). The assessment of the neural correlates of self-evaluation gained popularity to assess the self-concept in individuals with IGD. This attempt, however, seems to critically depend on the reliability of the investigated task-fMRI brain activation. As first study to date, we assessed test–retest reliability of an fMRI self-evaluation task. Test–retest reliability of neural brain activation between two separate fMRI sessions (approximately 12 months apart) was investigated in N = 29 healthy participants and N = 11 individuals with pathological internet gaming. We computed reliability estimates for the different task contrasts (self, a familiar, and an unknown person) and the contrast (self > familiar and unknown person). Data indicated good test–retest reliability of brain activation, captured by the “self”, “familiar person”, and “unknown person” contrasts, in a large network of brain regions in the whole sample ( N = 40) and when considering both experimental groups separately. In contrast to that, only a small set of brain regions showed moderate to good reliability, when investigating the contrasts (“self > familiar and unknown person”). The lower reliability of the contrast can be attributed to the fact that the constituting contrast conditions were highly correlated. Future research on self-evaluation should be cautioned by the findings of substantial local reliability differences across the brain and employ methods to overcome these limitations.
Stress is a major precipitating factor for psychiatric disorders and its effects may depend on its duration and intensity. Of note, there are differences in individual susceptibility to stress, with some subjects displaying vulnerability and others showing resistance. Furthermore, the ability to react to stressful-life events can alter the response to a subsequent new stressor. Hence, we investigated whether the vulnerability and resilience to the chronic mild stress (CMS) paradigm, in terms of the hedonic phenotype, are paralleled by a different response when facing a novel acute challenge. Specifically, rats submitted to CMS were stratified based on their sucrose intake into vulnerable (anhedonic rats showing reduce intake of sucrose) and resilient (rats not showing the anhedonic-like behavior) subgroups and then further exposed to an acute restraint stress (ARS). Then, neuronal activation was investigated by measuring the gene expression of early immediate (IEG) genes such as Arc and Cfos and early response (ERG) genes, such as Gadd45β , Sgk1 , Dusp1 , and Nr4a1 , in brain regions that play a crucial role in the stress response. We found that resilient rats preserve the ability to increase ERG expression following the ARS selectively in the ventral hippocampus. Conversely, such ability is lost in vulnerable rats. Interestingly, the recovery from the anhedonic phenotype observed in vulnerable rats after 3 weeks of rest from the CMS procedure also parallels the restoration of the ability to adequately respond to the challenge. In conclusion, these findings support the role of the ventral subregion of the hippocampus in the management of both chronic and acute stress response and point to this brain subregion as a critical target for a potential therapeutic strategy aimed at promoting stress resilience.
Black people and People of Color are disproportionately affected by racism and show increased rates of psychosis. To examine whether racialized migrant groups are particularly exposed to racism and therefore have higher risks for psychosis, this paper (1) systematically assesses rates of psychosis among racialized migrant groups concerning the country of origin, and (2) analyzes interviews regarding the association of racism experiences with psychosis-related symptoms in racialized Black people and People of Color populations in Germany. We present an umbrella review of meta-analyses that report the incidence of positive symptoms (e.g., hallucinations and delusions) and negative symptoms (e.g., apathy and incoherent speech) of diagnosed schizophrenia, other non-affective psychotic disorders (e.g., schizoaffective disorder) or first-episode psychosis among migrants by country of origin. We also report 20 interviews with first- and second-generation migrants racialized as Black and of Color in Germany to capture and classify their experiences of racism as well as racism-associated mental health challenges. In the umbrella review, psychosis risk was greatest when migration occurred from developing countries. Effect size estimates were even larger among Caribbean and African migrants. In the qualitative study, the application of the constant comparative method yielded four subordinate themes that form a subclinical psychosis symptomatology profile related to experiences of racism: (1) a sense of differentness, (2) negative self-awareness, (3) paranoid ideation regarding general persecution, and (4) self-questioning and self-esteem instability. We here provide converging evidence from a quantitative and qualitative analysis that the risk of poor mental health and psychotic experiences is related to racism associated with minority status and migration.
While psychiatric and physical comorbidities in severe mental illness (SMI) have been associated with increased mortality and poor clinical outcomes, problem has received little attention in low- and middle-income countries (LMICs). This study established the prevalence of psychiatric (schizophrenia, bipolar affective disorder, and recurrent major depressive disorder) and physical (HIV/AIDS, syphilis, hypertension and obesity) comorbidities and associated factors among 1201 out-patients with SMI (schizophrenia, depression and bipolar affective disorder) attending care at two hospitals in Uganda. Participants completed an assessment battery including structured, standardised and locally translated instruments. SMIs were established using the MINI International Neuropsychiatric Interview version 7.2. We used logistic regression to determine the association between physical and psychiatric comorbidities and potential risk factors. Bipolar affective disorder was the most prevalent (66.4%) psychiatric diagnoses followed by schizophrenia (26.6%) and recurrent major depressive disorder (7.0%). Prevalence of psychiatric comorbidity was 9.1%, while physical disorder comorbidity was 42.6%. Specific comorbid physical disorders were hypertension (27.1%), obesity (13.8%), HIV/AIDS (8.2%) and syphilis (4.8%). Potentially modifiable factors independently significantly associated with psychiatric and physical comorbidities were: use of alcohol for both syphilis and hypertension comorbidities; and use of a mood stabilisers and khat in comorbidity with obesity. Only psychiatric comorbidity was positively associated with the negative outcomes of suicidality and risky sexual behaviour. The healthcare models for psychiatric care in LMICs such as Uganda should be optimised to address the high burden of psychiatric and physical comorbidities.
Healthcare workers experienced high degree of stress during COVID-19. Purpose of the present article is to compare mental health (depressive and Post-Traumatic-Stress-Disorders—PTSD—symptoms) and epigenetics aspects (degree of methylation of stress-related genes) in front-line healthcare professionals versus healthcare working in non-COVID-19 wards. Sixty-eight healthcare workers were included in the study: 39 were working in COVID-19 wards (cases) and 29 in non-COVID wards (controls). From all participants, demographic and clinical information were collected by an ad-hoc questionnaire. Depressive and PTSD symptoms were evaluated by the Patient Health Questionnaire-9 (PHQ-9) and the Impact of Event Scale—Revised (IES-R), respectively. Methylation analyses of 9 promoter/regulatory regions of genes known to be implicated in depression/PTSD ( ADCYAP1, BDNF, CRHR1, DRD2, IGF2, LSD1/KDM1A, NR3C1, OXTR, SLC6A4 ) were performed on DNA from blood samples by the MassARRAY EpiTYPER platform, with MassCleave settings. Controls showed more frequent lifetime history of anxiety/depression with respect to cases ( χ ² = 5.72, p = 0.03). On the contrary, cases versus controls presented higher PHQ-9 ( t = 2.13, p = 0.04), PHQ-9 sleep item ( t = 2.26, p = 0.03), IES-R total ( t = 2.17, p = 0.03), IES-R intrusion ( t = 2.46, p = 0.02), IES-R avoidance ( t = 1.99, p = 0.05) mean total scores. Methylation levels at CRHR1, DRD2 and LSD1 genes was significantly higher in cases with respect to controls ( p < 0.01, p = 0.03 and p = 0.03, respectively). Frontline health professionals experienced more negative effects on mental health during COVID-19 pandemic than non-frontline healthcare workers. Methylation levels were increased in genes regulating HPA axis ( CRHR1) and dopamine neurotransmission ( DRD2 and LSD1 ), thus supporting the involvement of these biological processes in depression/PTSD and indicating that methylation of these genes can be modulated by stress conditions, such as working as healthcare front-line during COVID-19 pandemic.
Many so-called “high functioning” autistic individuals struggle with daily living skills, and have poorer than expected adult outcomes in employment, relationships, and quality of life. Significant discrepancies between non-verbal intelligence and emotional processing can be observed in autism, but the role of the magnitude of this gap in achieving potential psychosocial outcome is not known. Here, we show in a large group of participants ( n = 107), that only among those with an autism diagnosis ( n = 33), the gap between non-verbal intelligence (as measured by Raven’s matrices) and the ability to perform the Reading the Mind in the Eyes test significantly predicts self-perceived emotional/social difficulties as assessed by the Empathy Quotient. Our results suggest that it is specifically the magnitude of the gap between (high) levels of abstract reasoning skills and poor proficiency in reading emotions expressed by the eyes that predicts self-perceived difficulties in emotional and social interactions among adults with autism. A better understanding of the underlying causes of the discrepancy between potential and actual psychosocial outcomes is the first step toward developing the most appropriate support for this vulnerable population, and our study offers some potentially important insights in this regard.
Common knowledge implies that individuals engaging in outdoor sports and especially in regular and extreme mountaineering are exceptionally healthy and hardened. Physical activity in outdoor environments has a positive effect on physical and mental health. However, regular and/or extreme mountaineering might share similarities with behavioural addictions and could thus also have a negative impact on health. In this cross-sectional web-based questionnaire study, we collected data on exercise and mountaineering addiction (Exercise Addiction Inventory; original and adapted version for mountaineering; Exercise Dependence Scale adapted version for mountaineering). Further surveyed parameters included mountaineering habits, Risk-Taking Inventory, Sensation-Seeking/Emotion Regulation/Agency Scale (SEAS), resilience, self-perceived stress, physical activity in metabolic units and mental health. Comparisons were performed between individuals with symptoms of addiction to mountaineering (MA) and individuals without symptoms of addiction to mountaineering or sports in general (CO) using non-parametric analyses. We analysed data from 335 participants, n = 88 thereof with addiction to mountaineering (MA) and n = 247 control participants (CO). The MA group scored significantly higher with regards to self-perceived stress ( p < 0.001) and included a significantly higher number of individuals affected by symptoms of depression ( p < 0.001), symptoms of anxiety ( p < 0.001), symptoms of eating disorders ( p < 0.001), alcohol abuse or dependence ( p < 0.001), illicit drug abuse ( p = 0.050), or current and history of psychiatric disorders ( p < 0.001). Individuals with MA showed higher values in all SEAS subscales as well as increased risk-taking ( p < 0.001). Regular and extreme mountaineering can display features of a behavioural addiction and is associated with psychiatric disorders. Behavioural addiction in mountaineering is associated with higher levels of sensation-seeking, emotion regulation, and agency, as well as increased risk-taking.
It is generally recognized that there are sex differences in many aspects of schizophrenia. The main purpose of this study was to investigate the sex differences in the prevalence and clinical correlates of insomnia in patients with chronic schizophrenia.
A total of 957 patients who met the DSM-IV diagnostic criteria for schizophrenia were recruited in this cross-sectional study (male/female = 630/327). Demographic, clinical, and insomnia data were collected using self-reported questionnaires. Fasting blood samples were collected to evaluate the status of blood lipids. Psychopathological symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS).
The prevalence rate of insomnia in female patients with schizophrenia was significantly higher than that in male patients (17.3% for males and 26.3% for females; χ² = 10.74, p = 0.001). Regression analysis showed that in male patients, insomnia was independently associated with severe PANSS positive symptoms, severe PANSS depressive factor, and high levels of low-density lipoprotein levels, while in female patients, insomnia was associated with low education level, high PANSS depressive factor, and high levels of apolipoprotein B levels.
This study illustrates that insomnia is more frequent in female than male schizophrenia patients, and that there are differences in the clinical correlates of insomnia by sex, suggesting that sex differences should be considered in prevention and treatment strategies for coexisting insomnia in schizophrenia patients.
Negative symptoms are complex psychopathology. Although evidence generally supported the NIMH five consensus domains, research seldom examined measurement invariance of this model, and domain-specific correspondence across multiple scales. This study aimed to examine the interrelationship between negative symptom domains captured by different rating scales, and to examine the domain-specific correspondence across multiple scales. We administered the Brief Negative Symptom Scale (BNSS), the Self-evaluation of Negative Symptoms (SNS), and the Scale for Assessment of Negative Symptoms (SANS) to 204 individuals with schizophrenia. We used network analysis to examine the interrelationship between negative symptom domains. Besides regularized partial correlation network, we estimated bridge centrality indices to investigate domain-specific correspondence, while taking each scale as an independent community. The regularized partial correlation network showed that the SNS nodes clustered together, whereas the SANS and the BNSS nodes intermingled together. The SANS attention domain lied at the periphery of the network according to the Fruchterman–Reingold algorithm. The SANS anhedonia–asociality (strength = 1.48; EI = 1.48) and the SANS affective flattening (strength = 1.06; EI = 1.06) had the highest node strength and EI. Moreover, the five nodes of the BNSS bridged the nodes of the SANS and the SNS. BNSS blunted affect (strength = 0.76; EI = 0.76) and SANS anhedonia–asociality (strength = 0.76; EI = 0.74) showed the highest bridge strength and bridge EI. The BNSS captures negative symptoms and bridges the symptom domains measured by the SANS and the SNS. The three scales showed domain-specific correspondence.
Visual stress is thought to reflect cortical excitability and has been associated with many neurological, neuropsychiatric, and neurodevelopmental conditions. However, its relationships with symptoms of depression and anxiety have not yet been elucidated. We conducted two separate studies to first examine visual stress in a longitudinal community sample of 104 participants (aged 12–24) in association with prospective symptoms of depression, anxiety, and distress after 3 months, and subsequently in a cross-sectional epidemiological sample of 530 participants (aged 15–24) to validate its associations with current mood and distress symptoms. The Pattern Glare Test was used to examine visual stress to three grating patterns with the spatial frequencies (SF) of 0.3, 2.3, and 9.4 cycles per degree (cpd). Other known factors of mental health, including functioning, as well as resilience, hopelessness, and loneliness, were also assessed at baseline. In both studies, we showed that perceptual distortions were highest toward the pattern with mid-SF (2.3 cpd). Multiple linear regression analyses revealed that greater visual stress was significantly associated with not only baseline but also 3-month symptom outcomes, even when accounting for age, years of education, days of no functioning, resilience, hopelessness, and loneliness. Our findings suggest the importance of visual stress in understanding and predicting poor mental health outcomes. As mental health can lead to far-reaching consequences that extend to adulthood, our findings may inform state-of-the-art innovative strategies for the prediction of poor mental health outcomes and suggest visual stress as a potential marker for early risk detection among young people.
This study aims to investigate the role of cognitive function in the efficacy prediction of selective serotonin reuptake inhibitors (SSRIs) for depression patients and to further the understanding of the relationship between baseline cognitive function and depression trajectory.
This was part of a multicenter study for major depressive disorder. The study included 172 first-episode depression patients and 93 recurrent depression patients who had their cognitive function assessed at baseline and followed up for 8 weeks of SSRI treatment.
After constructing a 2-level hierarchical linear model with depression change- and cognitive function-level variables, the processing speed at baseline was the best predictor for the improvement of depression at each follow-up in first-episode patients (G11 = 0.03, P = 0.042). The treatment prediction model slope varied across patients depending on the processing speed scores at baseline. With the receiver operating characteristic curve, the combination of sociodemographic characteristics, sedative hypnotics, baseline 17-item Hamilton Rating Scale for Depression (HAMD17), and cognitive function showed the highest predictive power in major depressive disorder remission, resulting in a classification accuracy of 71.5%, a sensitivity of 82.5%, and a specificity of 55.1% (AUC = 0.713; P < 0.001).
Baseline cognitive function could help clinicians to better understand the trajectory of first-episode depression patients during acute treatment with SSRIs.
Severe mental disorders have been associated with increased COVID-19 mortality. The aim of this study was to evaluate the results of the vaccination campaign against COVID-19 after 1 year using exhaustive population-based data. In this nationwide population-based study, we used data from the French national medico-administrative database (SNDS) and the COVID Vaccine teleservice from January 4, 2021 (date of activation of the teleservice) to January 30th, 2022. As of January 30th, 2022, the rate of first injection in France was 80.2% (54 million people) and the rate of booster vaccination was 78.3% (52.7 million people). Except for opioid use disorder, all individuals with chronic illnesses or risk factors for poor COVID-19 outcome (e.g., smoking and obesity) had higher rates of vaccination than the general population (from 83.4 to 94.5% vs. 78.3%). However, the four diseases ranking last for both initial and booster vaccinations were mental disorders: alcohol use disorders (86 and 84.3%), neurodevelopmental psychiatric disorders (85.3 and 83.7%), schizophrenia-spectrum disorder (85 and 83.4%) and opioid use disorders (72.9 and 69.4%). Except for opioid disorders, all patients with mental disorders had higher rates of vaccination compared to the general population. However, these rates were lower than other chronic diseases at risk of severe COVID-19 outcomes. Vaccination campaigns must redouble their efforts to improve vaccination penetration in patients with mental disorders.
We aim to explore the combined effects of the smoking and breastfeeding on offspring mental health outcomes. We used data from UK biobank (N = 342,846) to evaluate joint effect of breastfeeding and maternal smoke during pregnancy (MSDP) on seven adult offspring mental health outcomes (self-reported depression, depression score, self-reported anxiety, anxiety score, neuroticism score, self-harm, suicide). We stratified individuals to MSDP group and non-MSDP group as well as breastfeeding group and non-breastfeeding group. Multiple linear regression and logistic regressions analysis were performed between independent variables (MSDP or breastfeeding) and dependent variables separately (seven mental health outcomes) in each stratum. Effect estimates were expressed as β values and OR values. Sex, age, 10 principle components of population structure, smoking, alcohol use, and Townsend deprivation index were examined as covariates. At MSDP grouping level, coefficients (odds ratio [OR]) for association of breastfed as a baby with self-reported anxiety (category variable) were 0.87 (95%CI, (0.82–0.93), P = 1.74 × 10–5) in the MSDP group and 0.83 (95%CI, (0.79–0.87), P = 2.76 × 10–17) in the non-MSDP group. At breastfeeding grouping level, OR for association of MSDP and self-reported anxiety were 1.15 (95%CI, (1.10–1.20), P = 5.36 × 10–11) in breastfeeding group and 1.12(95%CI, (1.06–1.20), P = 2.02 × 10–4) in non-breastfeeding group. At MSDP grouping level, negatively associations were found for breastfeeding and anxiety score (continuable variable) in MSDP group (-0.04 SD change per SD change in MSDP, 95% CI, (− 0.06, − 0.02), P = 2.42 × 10–3) and non-MSDP group (-0.06 SD change per SD change in MSDP, 95%CI, (− 0.07, − 0.04), P = 1.70 × 10–11). At breastfeeding grouping level, positive association was found for MSDP and anxiety score in the breastfeeding group (0.07 SD change per SD change in MSDP, 95%CI, (0.06–0.09), P = 1.49 × 10–20) and non-breastfeeding group (0.07 SD change per SD change in MSDP, 95%CI, (0.05–0.09), P = 7.19 × 10–8). Compared with non-MSDP group, the protective effect (reflected by coefficients) of breastfeeding on anxiety in the MSDP decreased. Our preliminary study found MSDP may lower the protective effect of breastfeeding on the adult offspring anxiety, depression and neuroticism, providing useful recommendations for health care service via quitting smoking during pregnancy and encouraging prolonged breastfeeding.
Research integrating molecular and imaging data provides important insights into how the genetic profile associated with dopamine signaling influences inter-individual differences in brain functions. However, the effects of genetic variations in dopamine signaling on the heterogeneity of brain changes induced by repetitive transcranial magnetic stimulation (rTMS) still remain unclear. The current study examined the composite effects of genetic variations in dopamine-related genes on rTMS-induced brain responses in terms of the functional network connectivity and working memory performance. Healthy individuals (n = 30) participated in a randomized, double-blind, sham-controlled study with a crossover design of five consecutive days where active rTMS or sham stimulation sessions were administered over the left dorsolateral prefrontal cortex (DLPFC) of the brain. Participants were mostly women (n = 29) and genotyped for polymorphisms in the catechol-O-methyltransferase and D2 dopamine receptor genes and categorized according to their genetic composite scores: high vs. low dopamine signaling groups. Pre- and post-intervention data of resting-state functional magnetic resonance imaging and working memory performance were obtained from 27 individuals with active rTMS and 30 with sham stimulation sessions. The mean functional connectivity within the resting-state networks centered on the DLPFC increased in the high dopamine signaling group. Working memory performance also improved with rTMS in the high dopamine signaling group compared to that in the low dopamine signaling group. The present results suggest that genetic predisposition to higher dopamine signaling may be a promising neurobiological predictor for rTMS effects on cognitive enhancement.
Trial registration: ClinicalTrials.gov (NCT02932085).
Schizophrenia spectrum disorders (SSDs) are presumed to be associated with retinal thinning. However, evidence is lacking as to whether these retinal alterations reflect a disease-specific process or are rather a consequence of comorbid diseases or concomitant microvascular impairment.
The study included 126 eyes of 65 patients with SSDs and 143 eyes of 72 healthy controls. We examined macula and optic disc measures by optical coherence tomography (OCT) and OCT angiography (OCT-A). Additive mixed models were used to assess the impact of SSDs on retinal thickness and perfusion and to explore the association of retinal and clinical disease-related parameters by controlling for several ocular and systemic covariates (age, sex, spherical equivalent, intraocular pressure, body mass index, diabetes, hypertension, smoking status, and OCT signal strength).
OCT revealed significantly lower parafoveal macular, macular ganglion cell–inner plexiform layer (GCIPL), and macular retinal nerve fiber layer (RNFL) thickness and thinner mean and superior peripapillary RNFL in SSDs. In contrast, the applied OCT-A investigations, which included macular and peripapillary perfusion density, macular vessel density, and size of the foveal avascular zone, did not reveal any significant between-group differences. Finally, a longer duration of illness and higher chlorpromazine equivalent doses were associated with lower parafoveal macular and macular RNFL thickness.
This study strengthens the evidence for disease-related retinal thinning in SSDs.
Youth with attention-deficit/hyperactivity disorder (ADHD) are at increased risk to develop co-morbid depression. Identifying factors that contribute to depression risk may allow early intervention and prevention. Poor emotion regulation, which is common in adolescents, is a candidate risk factor. Impaired cognitive emotion regulation is a fundamental characteristic of depression and depression risk in the general population. However, little is known about cognitive emotion regulation in youth with ADHD and its link to depression and depression risk. Using explicit and implicit measures, this study assessed cognitive emotion regulation in youth with ADHD (N = 40) compared to demographically matched healthy controls (N = 40) and determined the association with depressive symptomatology. As explicit measure, we assessed the use of cognitive emotion regulation strategies via self-report. As implicit measure, performance in an ambiguous cue-conditioning task was assessed as indicator of affective bias in the processing of information. Compared to controls, patients reported more frequent use of maladaptive (i.e., self-blame, catastrophizing, and rumination) and less frequent use of adaptive (i.e., positive reappraisal) emotion regulation strategies. This pattern was associated with the severity of current depressive symptoms in patients. In the implicit measure of cognitive bias, there was no significant difference in response of patients and controls and no association with depression. Our findings point to depression-related alterations in the use of cognitive emotion regulation strategies in youth with ADHD. The study suggests those alterations as a candidate risk factor for ADHD-depression comorbidity that may be used for risk assessment and prevention strategies.
Social functioning is impaired in severe mental disorders despite clinical remission, illustrating the need to identify other mechanisms that hinder psychosocial recovery. Affective lability is elevated and associated with an increased clinical burden in psychosis spectrum disorders. We aimed to investigate putative associations between affective lability and social functioning in 293 participants with severe mental disorders (schizophrenia- and bipolar spectrum), and if such an association was independent of well-established predictors of social impairments. The Affective Lability Scale (ALS-SF) was used to measure affective lability covering the dimensions of anxiety-depression, depression-elation and anger. The interpersonal domain of the Social Functioning Scale (SFS) was used to measure social functioning. Correlation analyses were conducted to investigate associations between affective lability and social functioning, followed by a hierarchical multiple regression and follow-up analyses in diagnostic subgroups. Features related to premorbid and clinical characteristics were entered as independent variables together with the ALS-SF scores. We found that higher scores on all ALS-SF subdimensions were significantly associated with lower social functioning (p < 0.005) in the total sample. For the anxiety-depression dimension of the ALS-SF, this association persisted after controlling for potential confounders such as premorbid social functioning, duration of untreated illness and current symptoms (p = 0.019). Our results indicate that elevated affective lability may have a negative impact on social functioning in severe mental disorders, which warrants further investigation. Clinically, it might be fruitful to target affective lability in severe mental disorders to improve psychosocial outcomes.
Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.
The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini‐International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19–2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.
Schizotypy constitutes a susceptibility to beneficial and deleterious schizotypal traits, ranging from coping mechanisms to schizotypal personality disorder on a psychosis continuum. Growing evidence indicates a relationship between childhood adversity and trauma and schizotypy. However, the exact influence of childhood adversity and trauma on schizotypy and its relation to sex is not sufficiently understood. Therefore, we investigated sex-adjusted connections between childhood adversity and trauma subdomains (emotional/physical/sexual abuse, emotional/physical neglect) and positive (magical ideation, perceptual aberration) as well as negative schizotypy (physical/social anhedonia). In total, 240 outpatients of the Early Detection and Intervention Centre of the University Hospital Cologne were assessed with the Trauma and Distress Scale for childhood adversity and trauma and the Wisconsin Schizotypy Scales for schizotypy. Path analyses were performed to investigate sex-adjusted correlations. The well-fitting path model of the total sample linked emotional abuse to magical ideation (p = 0.03; SE = 0.20) and emotional neglect to social anhedonia (p = 0.01; SE = 0.26). In females, physical abuse predicted magical ideation (p = 0.01; SE = 0.33), while emotional neglect forecasted physical anhedonia (p = 0.03; SE = 0.34) and social anhedonia (p = 0.03; SE = 0.32). In males, sexual abuse predicted perceptive aberration (p = 0.04; SE = 0.19) and emotional abuse forecasted magical ideation (p = 0.03; SE = 0.27). Overall, the significance of sex-specific interrelations between trauma and schizotypy were highlighted. Magical ideation and perceptive aberration occurred prominently in the absence of negative and disorganized schizotypy, thus positive schizotypy could be discussed as a beneficial expression of coping with emotional, physical and sexual abuse. Furthermore, emotional neglect should be addressed particularly to prevent deleterious negative schizotypy in females.
Trial registration number (20-1243), date of registration (May 19th 2020), retrospectively registered.
While the COVID-19 pandemic continues, patients with pre-existing mental disorders are increasingly recognized as a risk group for adverse outcomes. However, data are conflicting and cover only short time spans so far. Here, we investigate the medium-term and peri-lockdown-related changes of mental health outcomes in such patients in a longitudinal study. A cohort of 159 patients comprising all major mental disorders (ICD-10 F0-F9) were interviewed twice with the Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) to evaluate psychosocial burden, psychiatric symptoms and resilience at the end of the first (April/May 2020) and the second lockdown in Germany (November/December 2020). For the primary outcome “psychosocial burden” ratings also comprised retrospective pre-pandemic (early 2020) and very early states during the pandemic (March 2020). For all diagnostic groups, psychosocial burden varied significantly over time (p < 0.001) with an increase from the pre-pandemic to the initial phase (p < 0.001), followed by a steady decrease across both lockdowns, normalizing in November/December 2020. Female gender, high adjustment disorder symptom load at baseline and psychiatric comorbidities were risk factors for higher levels and an unfavorable course of psychosocial burden. Most psychiatric symptoms changed minimally, while resilience decreased over time (p = 0.044 and p = 0.037). The longitudinal course of psychosocial burden indicates an initial stress response, followed by a return to pre-pandemic levels even under recurrent lockdown conditions, mimicking symptoms of an adjustment disorder. Strategies for proactive, specific and continuous treatment have to address resilience capacities before their depletion in the pandemic aftermath, especially for patients with additional risk factors.
Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12–18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months’ time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents.
Co-occurrence of mental disorders including severe PTSD, somatic symptoms, and dissociation in the aftermath of trauma is common and sometimes associated with poor treatment outcomes. However, the interrelationships between these conditions at symptom level are not well understood. In the present study, we aimed to explore direct connections between PTSD, somatic symptoms, and dissociation to gain a deeper insight into the pathological processes underlying their comorbidity that can inform future treatment plans. In a sample of 655 adult inpatients with a diagnosis of severe PTSD following childhood abuse (85.6% female; mean age = 47.57), we assessed symptoms of PTSD, somatization, and dissociation. We analyzed the comorbidity structure using a partial correlation network with regularization. Mostly positive associations between symptoms characterized the network structure. Muscle or joint pain was among the most central symptoms. Physiological reactivation was central in the full network and together with concentrations problems acted as bridge between symptoms of PTSD and somatic symptoms. Headaches connected somatic symptoms with others and derealization connected dissociative symptoms with others in the network. Exposure to traumatic events has a severe and detrimental effect on mental and physical health and these consequences worsen each other trans-diagnostically on a symptom level. Strong connections between physiological reactivation and pain with other symptoms could inform treatment target prioritization. We recommend a dynamic, modular approach to treatment that should combine evidence-based interventions for PTSD and comorbid conditions which is informed by symptom prominence, readiness to address these symptoms and preference.
The onset of bipolar disorder (BD) occurs in childhood or adolescence in half of the patients. Early stages of BD usually present depressive episodes, which makes it difficult to be distinguished from major depressive disorder (MDD). Objective biomarkers for discriminating BD from MDD in adolescent patients are limited. We collected basic demographic data and the information of the first blood examination performed after the admission to psychiatry unit of BD and MDD inpatients during 2009–2018. We recruited 261 adolescents (aged from 10 to 18), including 160 MDD and 101 BD. Forward-Stepwise Selection of binary logistic regression was used to construct predictive models for the total sample and subgroups by gender. Independent external validation was made by 255 matched patients from another hospital in China. Regression models of total adolescents, male and female subgroups showed accuracy of 73.3%, 70.6% and 75.2%, with area under curves (AUC) as 0.785, 0.816 and 0.793, respectively. Age, direct bilirubin (DBIL), lactic dehydrogenase (LDH), free triiodothyronine (FT3) and C-reactive protein (CRP) were final factors included into the models. The discrimination was well at external validation (AUC = 0.714). This study offers the evidence that accessible information of common clinical laboratory examination might be valuable in distinguishing BD form MDD in adolescents. With good diagnostic accuracies and external validation, the total regression equation might potentially be applied to individualized clinical inferences on adolescent BD patients.