Annals of General Psychiatry最新文献

Schizophrenia is a complex, heterogeneous, and highly disabling severe mental disorder whose pathogenesis has not yet been fully elucidated. Epigenetics, as a bridge between genetic and environmental factors, plays an important role in the pathophysiology of schizophrenia. Over the past decade, epigenetic-wide association studies have rapidly become an important branch of psychiatric research, especially in deciphering the molecular mechanisms of schizophrenia. This review systematically analyzes recent advances in epigenome-wide association studies (EWAS) of schizophrenia, focusing on technological developments. We synthesize findings from large-scale EWAS alongside emerging evidence on DNA methylation patterns, histone modifications, and regulatory networks, emphasizing their roles in disease mechanisms and treatment responses. In addition, this review provides a prospective outlook, evaluating the impact that technological developments may have on future studies of schizophrenia. With the continuous advancement of high-throughput sequencing technology and the increasing maturity of big data analysis methods, epigenetics is expected to have a significant impact on the early diagnosis, prognosis assessment and even personalized treatment of schizophrenia.

Background: Genetic susceptibility to mental health and cognitive traits, as well as air pollution, significantly impact cognition. The interplay between polygenic liability and fine particulate matter (PM_2.5) remains unclear due to the limited number of large-scale studies in Asia. This study utilized the Taiwan Biobank, a nationwide community-based database, to investigate the main and modified effect of PM_2.5 on individuals' polygenic susceptibility in cognition.

Methods: Polygenic risk score (PRS) for cognitive performance (CP PRS), Alzheimer's disease (AD PRS), schizophrenia (SCZ PRS), and major depression (MDD PRS) were computed representing genetic susceptibility for an individual. APOE genotype was classified into E3/E3, E3/E4, and E4/E4. The five-year average concentration of PM_2.5 from satellite images was used for defining environmental exposure. Cognitive performance was evaluated via the Mini-Mental State Examination (MMSE) score. The association between personal genetic susceptibility, PM_2.5, and cognitive performance was examined using multilevel linear regression with the adjustment of age, sex, batch effect, and population stratification effect. The gene-environment synergism was examined with the inclusion of product term of PM_2.5 and PRS in the multivariate model.

Results: Our analyses included 25,593 participants from 164 townships. Participants exposed to higher PM_2.5 concentrations had a lower MMSE score (Beta=-0.0830 corresponding to a 1 µg/m³ increase in PM_2.5 concentration, 95% CI, -0.0973 to -0.0688, p-value < 0.0001). After controlling for PM_2.5 concentration, CP PRS (Beta = 0.1729, 95% CI, 0.1470 to 0.1988, p-value < 0.0001), SCZ PRS (Beta=-0.0632, 95% CI, -0.0891 to -0.0374, p-value < 0.0001), and AD PRS (Beta=-0.0321, 95% CI, -0.0580 to -0.0062, p-value = 0.0153) were associated with MMSE score. After further examination of gene-environment synergism, no interaction effect was identified, indicating different mechanism of PM_2.5 and genetic liability to influence cognitive performance.

Conclusions: Human polygenic loading and PM_2.5 may impact cognition via an independent pathway. A prevention strategy targeting air pollution reduction may effectively improve the cognitive performance. Multiple exposures and their influences on the long-term change of cognition were required in future research.

Background: The predominant polarity in bipolar disorder (BD) is defined by the skewness of mood episodes towards either the manic or depressive pole. However, since the predominant polarity can only be established over the long term, it is crucial to identify predictors of illness trajectory. Among these factors, the polarity at onset has been suggested to hold important implications, even though research in this field is not entirely consistent so far. In this retrospective study, we thus explored whether the polarity of the first episode can predict the predominant polarity in BD.

Methods: We included subjects with BD consecutively referred to two acute inpatient units in the Milan metropolitan area from May 2020 to January 2024. Following Barcelona criteria, a manic (mPP) and a depressive (dPP) predominant polarity were defined as having a ratio ≥ 2:1 of past manic/hypomanic or depressive episodes, respectively. The relationship between first episode polarity and either mPP or dPP was examined using multivariable logistic regression models. A path analysis was then performed to jointly test the associations between putative variables and the predominant polarity.

Results: This study included 128 participants. Regression models estimated an association between a manic onset and a mPP (β = 3.23, p < 0.001) as well as between a depressive onset and a dPP (β = 3.65, p < 0.001). Participants with a mPP showed a lower age at onset (β = - 0.13, p = 0.004), while subjects diagnosed with BD type I were less likely to show a dPP (β = - 2.09, p = 0.024). The path analysis highlighted an association between earlier onset and the likelihood of a first episode of manic polarity (coeff. = - 1.39, p = 0.021). A manic onset was associated with a higher likelihood of mPP (coeff. = 3.46, p < 0.001) and a lower likelihood of dPP (coeff. = - 3.71, p < 0.001). Consistently, participants with a manic onset were more likely to experience a lower number of depressive episodes (coeff. = - 1.36, p < 0.001). Finally, cannabis use disorder was associated with a lower number of depressive episodes (coeff. = - 0.57, p = 0.011).

Conclusions: These results provide important insights into the likely predictive value of first episode polarity in relation to the predominant polarity in BD. Though future studies validating these findings are needed, the polarity at onset may serve as an early marker for illness trajectory.

Background: Depression occurring during the perinatal period (PND) could affect both future mother and father. PND may lead to several adverse physical and mental health outcomes for the whole family. Several psychopathological determinants have been identified, even though few studies investigated the role of paternal mental health in the onset of maternal perinatal depression (MPND). Hence, a retrospective cohort study was carried out in order to investigate the relationship between paternal mental health and the occurrence of antenatal maternal depression as well as identifying potential sociodemographic, clinical and obstetrical predictors in the development of MPND.

Methods: All pregnant women afferent to the Perinatal Mental Health Outpatient Service of the Unit of Clinical Psychiatry at the University Hospital of Marche, Polytechnic University of Marche, Ancona, Italy, between April 2021 to February 2022, were consecutively recruited and longitudinally screened for antenatal depression. The sample was divided in two groups, based on the screening by using the Edinburgh Postpartum Depression Scale (EPDS) for PND. A stepwise binary logistic regression analysis was performed in order to evaluate the predictors associated with the presence of antenatal depression (vs. the absence of antenatal depression).

Results: A total of 106 participants among all 460 screened from April 2021 to February 2022, were retrospectively included. In our sample, a prevalence of 13.2% in antenatal depression was found. The binary logistic regression model showed that the higher maternal age (OR = 1.320; p = 0.005), gestational comorbidity (OR = 10.931; p = 0.010), pregnant women's (OR = 19.001; p = 0,001) and their partner's positive history (OR = 16.536; p = 0.004) for mental disorder significantly predicted the presence of antenatal depression in our sample.

Conclusions: Our study suggests the need to investigate the pre-existing psychopathology of the pregnant woman's partner as a potential risk factor for MPND, particularly for antenatal depression. Overall, a better understanding and investigation of all potential risk and/or protective factors for the onset and/or maintenance and/or worsening of MPND could help clinicians in early identifying treatment strategies to improve maternal mental health as well as future father's mental health.

Background: Anxiety disorders (ADs) are common among children and adolescents and frequently co-occur with specific learning disorder (SLD). Approximately 20% of children with SLD meet criteria for ADs, while those with anxiety are six times more likely to have a premorbid SLD. The strong relationship between premorbid SLD and ADs underscores the importance of examining developmental trajectories and manifestations of neuropsychiatric conditions like ADs, particularly when SLD is present. In this context, this study investigates the clinical profiles of children and adolescents with a first diagnosis of an AD and a history of SLD compared to those with a first diagnosis of an AD without a history of SLD. The analysis focuses on various clinical characteristics, including developmental history, demographic aspects, age of anxiety onset, global functioning, types of ADs, self-report anxiety and depressive symptoms, and adaptive behavior. Additionally, the study aims to explore the relationship between anxiety symptoms and depressive symptoms, adaptive behavior, and age.

Methods: We conducted a cross-sectional, retrospective study with 78 participants from the Child and Adolescent Neuropsychiatry Unit, divided into two groups: those with ADs alone (Group AD, n = 42) and those with both ADs and premorbid SLD (Group AD + SLD, n = 36). We collected data on developmental history, demographic information, age of anxiety onset, global functioning, anxiety and depressive symptoms, and adaptive behavior.

Results: Our findings revealed that Group AD experienced more stressful life events and had higher cognitive levels, whereas Group AD + SLD showed a greater impairment in global functioning. Notably, Group AD exhibited lower social adaptive behavior and higher self-reported anxiety and depressive symptoms than Group AD + SLD, possibly indicating a greater awareness of their emotional distress.

Conclusions: These findings highlight the impact of premorbid neurodevelopmental disorders into clinical manifestations of psychopathological symptoms. In particular, results underline the importance of developing tailored clinical interventions for children with co-occurring ADs and learning difficulties, focusing more on their emotional awareness to better address the unique challenges posed by the comorbidity.

Background: Desvenlafaxine, a serotonin-norepinephrine reuptake inhibitor, has demonstrated efficacy in improving affective symptoms of Major Depressive Disorder (MDD); however, its effects on associated cognitive and functional difficulties remain underexplored. This study seeks to assess the antidepressant effects of desvenlafaxine in patients with SSRI-resistant MDD, its impact on both objective and subjective cognitive performance, where cognitive improvements occur independently of clinical recovery or not, and its influence on psychosocial functioning.

Methods: An observational case-control prospective study with 66 participants was conducted, including 26 patients with a current MDD episode, with an inadequate SSRI response, and with the prescription of desvenlafaxine as the next antidepressant therapeutic option, and 40 healthy controls. Sociodemographic, clinical, cognitive, and functional assessments were conducted both before and after a 12-week treatment period. Changes were analyzed using two tailed paired-samples t-tests, with Cohen's d for effect sizes. Cognitive improvements were compared between the patients who achieved remission and those who did not.

Results: Patients showed significant improvements in depressive and anxiety symptoms, attention/working memory and processing speed, self-perceived cognitive difficulties and psychosocial functioning. Highlighting the fact these cognitive enhancements occurred independently of patients' clinical improvement.

Conclusions: The findings of this study focus on the therapeutic potential of desvenlafaxine, demonstrating its efficacy not only in ameliorating clinical and functional symptoms but also in addressing specific cognitive impairments in patients with depression. Further research is needed to elucidate the mechanisms underlying desvenlafaxine's effects and optimize treatment strategies for individuals with MDD.

Trial registration number: NCT03432221 (clinical.

Trials: gov). Registration date: 08-01-2018.

Globally, major depressive disorder, or MDD, is a leading cause of disability. It negatively impacts social interactions and significantly limits daily functioning, ultimately reducing life satisfaction. The prevalence rate is about twice as high in women as in males. It is believed that the genesis of major depressive disorder is complicated and includes biological, genetic, environmental, and psychological factors. Mental pain, although distinguishable, constitutes a crucial framework in major depressive disorder (MDD) as the pair may precipitate suicide risk. Mental pain, as conceptualized in Panksepp's emotional theory, is especially relevant when considering the key role of the opioid system, which can influence feelings tied to grief and separation. There has been a renewed interest in targeting the opioid system for antidepressant treatment in MDD and to soothe mental pain. Antidepressant drugs endowed with partial mu-opioid receptor (MOR) agonism and kappa-opioid receptor (KOR) antagonism might represent novel pharmacological tools to address unmet needs in MDD patients. The combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults affected by MDD. We hypothesized that dextromethorphan-bupropion could impact the reduction of mental pain in MDD patients by targeting the opioid system, as supported by Panksepp's theory. The combination of dextromethorphan with bupropion might deal with various aspects of mental pain, possibly improving treatment results.

Background: The growing popularity of internet gaming among adolescents and young adults has driven an increase in both casual and excessive gaming behavior. Nevertheless, it remains unclear how progressive increases in internet gaming engagement led to changes within and between brain networks. This study aims to investigate these connectivity alterations across varying levels of gaming involvement.

Methods: In this cross-sectional study, 231 participants were recruited and classified into three groups according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Internet Gaming Disorder (IGD): IGD group, highly engaged gaming(HEG) group, and lowly engaged gaming (LEG) group. Resting-state fMRI data from 217 participants (143 males, 74 females) were included in the final analysis. Independent component analysis was used to examine differences in intra- and inter-network functional connectivity (FC)across the three groups.

Results: No significant differences were found in intra-network FC across the three groups. However, significant inter-network differences between the dorsal attention network(dAN)and the visual network (VN) among the three groups were observed. The HEG group exhibited significantly higher dAN-VN functional network connectivity (FNC) compared to the LEG group. Linear correlation analyses showed no significant correlation between the dAN-VN FNC values and IGD-20T scores.

Conclusion: Throughout the development of IGD, increasing levels of engagement are associated with a rise and subsequent decline in FNC of DAN-VN. This pattern may reflect top-down attentional regulation in the early stages of addiction, followed by attentional bias as addiction progresses.

Background: Schizophrenia is a highly heterogeneous disease, and a high percentage of patients are at high risk of developing somatic comorbidities, which must be taken into account in disease management and treatment selection.

Main body: Antipsychotics are often associated with side effects that worsen the somatic comorbidities. Among the different options, cariprazine is generally safe and usually well tolerated in both acute and long-term treatment and is often a good choice when balancing clinical benefits and side effects. Given the lack of consensus on the priority of symptoms to treat and the reasons for switching therapy based on the balance between side effects and symptom resolution, twelve psychiatrists met for an expert meeting to discuss the most common and worrisome antipsychotic side effects leading to switching, the most important somatic comorbidities, and the best way to address specific symptoms in both the acute and maintenance phases of treatment in schizophrenia. Special attention was given to metabolic comorbidities, sexual dysfunction, and cardiovascular disease. This paper aims to examine the relationship between schizophrenia and specific somatic comorbidities, to discuss how the balance between efficacy and tolerability influences treatment choice in the acute and maintenance treatment of schizophrenia, and how these two variables may have different priorities at different stages of treatment.

Conclusion: The choice of treatment is based primarily on efficacy and tolerability. Cariprazine is beneficial in patients with positive and negative symptoms, and it has a side-effect profile with low rates of metabolic side effects, sedation, and sexual dysfunction.

Background: This study sought to investigate the prevalence, correlates, and network structure of the manifested symptoms in gambling disorder (GD) among methamphetamine (MA) use disorder (MUD) patients in China.

Methods: We interviewed 1069 patients using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA), Chinese version. Besides MA and other substance use disorders, GD was also ascertained by SSADDA. Other psychiatric diagnoses were ascertained, including major depressive episodes (MDEs), antisocial personality disorder, suicide and self-harm, and environmental factors, including childhood experiences.

Results: Of 1069 participants, 711 met the DSM-5 diagnostic criteria for MUD. Among the 711 participants with MUD, 52.3% met DSM-5 diagnostic criteria for GD. We found that alcohol use together with MA, childhood violent experiences, MDEs, severe MUD, and gambling duration significantly differed between MUD participants with and without GD. In the GD-MUD network, the central symptoms were gambling preoccupation (GD1), giving up important activities (MUD6), financial trouble (GD9), and MA tolerance (MUD5). MA tolerance (MUD5) also served as a bridge symptom across the network, exhibiting substantial associations with gambling preoccupation (GD1).

Conclusion: GD is prevalent among individuals in treatment for MUD in China. Network analysis suggests that gambling preoccupation and MA tolerance represent central features, and that MA tolerance serves as a bridge across GD and MUD.