Abstract

Schizophrenia (SCZ) and obsessive–compulsive disorder (OCD) typically have distinct diagnostic criteria and treatment approaches. SCZ is characterized by delusions, hallucinations, disorganized speech, and cognitive impairments, while OCD involves persistent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions). The co-occurrence of these disorders increases clinical complexity and poses significant challenges for diagnosis and treatment. Epidemiological studies indicate a significant overlap, with prevalence rates of comorbid OCD in SCZ patients ranging from 12% to 25%, which is higher than in the general population. Etiological hypotheses suggest shared genetic, neurobiological, and environmental factors, with genetic studies identifying common loci and pathways, such as glutamatergic and dopaminergic systems. Neuroimaging studies reveal both overlapping and distinct neural abnormalities, indicating shared and unique neurobiological substrates. Environmental factors, like early life stressors and urbanicity, also contribute to the comorbidity. The overlapping clinical features of both disorders complicate diagnosis. Treatment approaches include combining SSRIs with antipsychotics and cognitive behavioral therapy (CBT). The complexity of SCZ and OCD comorbidity underscores the need for a dimensional, spectrum-based perspective on psychiatric disorders, alongside traditional categorical approaches, to improve diagnosis and treatment outcomes.

Introduction

Schizophrenia (SCZ) and obsessive–compulsive disorder (OCD) are both debilitating psychiatric conditions, each with distinct diagnostic criteria and treatment approaches. SCZ, as defined in the DSM-5 [1], is a chronic mental disorder characterized by a range of symptoms, including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and cognitive impairments [2,3]. These symptoms must be present for a significant portion of time during a one-month period, with continuous signs of disturbance persisting for at least six months, significantly impacting various areas of functioning, such as work, interpersonal relations, and self-care [1]. SCZ’s influence on everyday life can be profound, often leading to significant disabilities and incomplete recovery for many individuals [4]. Those with relatively positive outcomes still contend with social isolation, the stigma associated with the disorder, and fewer opportunities to build close relationships. Unemployment rates are exceptionally high among those with SCZ [5,6]. Common issues, such as unhealthy diet, weight gain, smoking, and substance abuse, contribute to a decreased life expectancy, shortening it by about 13 to 15 years [5,6]. Moreover, the risk of suicide over a lifetime for individuals with SCZ is estimated to be between 5% and 10% [7].

OCD, on the other hand, involves persistent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions) aimed at reducing the anxiety generated by these thoughts [8,9]. Obsessions are defined as recurrent and persistent thoughts, urges, or images that are experienced as intrusive and unwanted, causing marked anxiety or distress. Compulsions are defined as repetitive behaviors or mental acts that an individual feels driven to perform in response to an obsession or according to rigid rules and as being time-consuming or causing significant distress or impairment in important areas of functioning [1]. OCD profoundly affects daily life, causing significant distress and impairment. Individuals with OCD often devote excessive time to their obsessions and compulsions, disrupting work, education, and personal relationships [10]. The disorder severely limits social and occupational functioning, with studies indicating that up to 60% of those with OCD experience moderate to severe daily impairment [10,11]. The quality of life for these individuals is considerably lower than that of the general population, with high comorbidity rates for depression and anxiety [9,10]. Regarding mortality, OCD is linked to a heightened risk of suicide; the lifetime prevalence of suicidal thoughts among individuals with OCD ranges from 36% to 63%, and the risk of suicide attempts is between 10% and 27% [12].

Discussion

The literature shows various overlapping factors between SCZ and OCD. Both disorders are fundamental pathological entities in psychiatry, due to their prevalence and the burden they impose [11,15,16,17,18]. They share a complex etiological and pathophysiological component, comprising genetic, environmental, and neurostructural elements [23,38,54,82]. Our review highlights how some of these elements demonstrate the following commonalities: shared genetic factors, environmental circumstances that may underlie both disorders, and shared neurostructural alterations. It is important, therefore, to consider studies that demonstrate common etiological and clinical characteristics. For example, a recent study using integrated bioinformatic analysis has highlighted shared genetic and molecular mechanisms between SCZ and OCD [119].

Due to the shared features and differing elements between the two disorders, treatment remains challenging. The pharmacological profiles of treatments for SCZ and OCD differ significantly, with SGAs potentially inducing obsessive symptoms by antagonizing the 5HT2A receptor [90]. Hence, further studies are necessary to determine the best treatment for OCSs in patients with schizophrenia. Preliminary recommendations include combining an antipsychotic with an SSRI, such as escitalopram [95].

Abstract

A molecular clock in the suprachiasmatic nucleus of the anterior hypothalamus, which is entrained by the dark-light cycle and controls the sleep-wake cycle, regulates circadian rhythms. The risk of developing mental disorders, such as schizophrenia, has long been linked to sleep abnormalities. Additionally, a common aspect of mental disorders is sleep disturbance, which has a direct impact on the intensity of the symptoms and the quality of life of the patient. This relationship can be explained by gene alterations such as CLOCK in schizophrenia which are also important components of the physiological circadian rhythm. The function of dopamine and adenosine in circadian rhythm should also be noted, as these hypotheses are considered to be the most popular theories explaining schizophrenia pathogenesis. Therefore, determining the presence of a causal link between the two can be key to identifying new potential targets in schizophrenia therapy, which can open new avenues for clinical research as well as psychiatric care. We review circadian disruption in schizophrenia at the genetic, metabolic, and clinical levels. We summarize data about clock and clock-controlled genes’ alterations, neurotransmitter systems’ impairments, and association with chronotype in schizophrenia patients. Our findings demonstrate that in schizophrenia either homeostatic or circadian processes of sleep regulation are disturbed. Also, we found an insufficient number of studies aimed at studying the relationship between known biological phenomena of circadian disorders and clinical signs of schizophrenia.

Introduction

Circadian rhythms are about 24-h variations in physiology and behavior that have developed through the course of phylogeny to help organisms anticipate daily environmental changes like the light/dark cycle. The suprachiasmatic nucleus (SCN), located in the anterior region of the hypothalamus, contains a molecular clock that regulates circadian rhythms and is entrained by the dark-light cycle. Circadian locomotor output cycles kaput protein (CLOCK), brain and muscle ARNT -like 1 (BMAL1), period circadian regulators 1 and 2 (PER1 and PER2), and cryptochrome circadian regulators 1 and 2 (CRY1 and CRY2) are some of the core clock genes that make up the molecular clockwork. The transcription-translation feedback loop that controls these genes oscillates every 24 h (Caba et al., 2018; Takahashi, 2017).

Almost every cell in the body contains this fundamental clock machinery (Dibner et al., 2010). A network of cell-autonomous circadian oscillators controls rhythmic outputs owing to the coordination of peripheral clocks by the master circadian pacemaker in the SCN. The principal time cue or “zeitgeber” for the entrainment of the clock to environmental changes is a perception of light input directly from the retina by SCN through the retinohypothalamic tract. The sleep-wake cycle is one of these rhythms governed by the circadian system, but it is also regulated by physiological sleep pressure, which builds up during waking and decreases during sleep (Ashton and Jagannath, 2020; Kandeger et al., 2021). Peripheral clock genes are also entrained by various time cues such as feeding rhythms and daily activity. Altered signaling of time cues may change the rhythms of both peripheral and central clock genes and even result in their uncoupling (Fedchenko et al., 2022).

Conclusions and future perspectives

Circadian rhythms have evolved throughout phylogeny to allow organisms to predict daily environmental changes, such as the light/dark cycle. Additionally, important to consider is its role in sleep regulation. Sleep disturbances are a common feature of several psychiatric pathologies such as schizophrenia. These disorders and their association with sleep disturbances can emerge as a potential therapeutic target and warrant further investigation. We demonstrated that in schizophrenia either homeostatic or circadian processes of sleep regulation are disturbed. Patients with schizophrenia show a higher prevalence of circadian rhythm disturbances in comparison to the general population.

In conclusion, the potential link between being born at certain times of the year and increased risk of developing schizophrenia has been extensively studied. Studies have suggested that exposure to high levels of UVR at certain times, as well as disruptions of circadian rhythms due to factors such as season of birth, socioeconomic status, and sleep disturbances during pregnancy, may be a risk factor. However, recent research has indicated that the month of conception, rather than the month of birth, may be more critical in the development of schizophrenia. Moreover, changes in eating behavior and meal timing can lead to changes in the circadian release of endocrine hormones.

Abstract

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia’s development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

Schizophrenia

Schizophrenia is a complex, heterogeneous psychiatric disorder influenced by both genetic and environmental factors, with a lifetime prevalence of approximately 1 % in the general population [1] . This condition manifests through a spectrum of symptoms: (i) positive symptoms such as delusions, hallucinations, paranoia, thought disorders, and psychomotor agitation; (ii) negative symptoms including emotional blunting, social withdrawal, and deficits in motivation and reward processing; (iii) cognitive impairment affecting learning, attention, executive function, and memory, particularly working memory [2] , [3] . Mood disturbances such as depression and anxiety are also common among patients.

The pathogenesis of schizophrenia is currently explained by several theories, the most notable being the dopaminergic hypothesis. This hypothesis proposes that positive symptoms arise from dysregulated dopaminergic neurotransmission in the limbic system of the midbrain, while disruptions in cortical pathways contribute to negative symptoms [4] . The glutamatergic hypothesis posits that changes in NMDA receptor-mediated glutamatergic transmission affect prefrontal neuronal connectivity [5] , and the serotonergic hypothesis attributes disturbances in neuronal activity to serotonin overload from the dorsal raphe nucleus serotonergic hypothesis suggests that stress causes overload of serotonin from the dorsal raphe nucleus [6] . The GABAergic hypothesis suggests that an imbalance between cortical excitation and inhibition, driven by disruptions in GABAergic neurotransmission, underlies the disorder [7] . Additionally, nicotinic receptors play a role in cholinergic transmission; studies have shown that nicotine can improve attention and memory performance in schizophrenic patients [8] . Cognitive dysfunction, a core feature observed in over 80 % of individuals with schizophrenics, involves multiple brain regions, including the dorsolateral and medial prefrontal cortices and the parietal regions [9] , [10] , [11] . Structural abnormalities in the medial temporal lobe, particularly the hippocampus, have been linked to memory deficits and play a significant role in the neural networks responsible for memory and spatial navigation [12] , [13] , [14] , [15] , [16] .

Abstract

Violent offending committed by people with schizophrenia has been a public concern. The present study aims to examine the incidence of violent offending among people with schizophrenia and its correlations with mental health resources and economic factors. In this study, an examination of violent offending by people with schizophrenia and those identified as not criminally responsible on account of mental disorder (NCRMD) between 2010 and 2019 in China’s Hunan province was undertaken. Principal component analysis (PCA) and regression analyses were used to explore the association of violent offending in people with schizophrenia and those identified as NCRMD with violent offending in the general population, mental health medical resources, and provincial GDP. Between 2010 and 2019, a total of 2,093 people with schizophrenia committed violent offending in Hunan province, including 1,374 (65.6%) cases identified as NCRMD. Over the period, the incidence of violent offending in people with schizophrenia and those identified as NCRMD has been decreasing. The incidences were positively correlated with the incidence of violent offending in the general population and negatively associated with mental health resources and provincial GDP. These findings may be valuable in helping to develop strategies for violence prevention and risk management for people with schizophrenia.

Introduction

Violence related to mental disorders has been a public health concern across the world. Evidence suggests that the risk of violent offending in people with schizophrenia is higher than that in the general population ( Fazel et al., 2014 ; Whiting et al., 2022 ), although most people with schizophrenia never engage in violence throughout their life ( Nielssen and Large, 2010 ; Strassnig et al., 2020 ). The consequences of violent behavior perpetrated by people with schizophrenia may impose a high economic burden on public healthcare services ( Senior et al., 2020 ). Therefore, it is critical to understand the trends in violent offending by people with schizophrenia as well as the systems-level factors including health and socio-economic characteristics, which will be valuable in helping to develop strategies for violence prevention and risk management for people with schizophrenia.

Existing studies examining the trends and patterns of violent offending related to mental disorders are mainly based in Western developed countries, and they also yielded inconsistent results. Earlier evidence suggested that the incidence of homicide related to mental disorders tended to remain stable, regardless of whether the overall rate of homicide in the general population decreased ( Flynn et al., 2021 ; Penney et al., 2018 ) or increased ( Taylor and Gunn, 1999 ). Some other studies have shown that the incidence of mental illness-related homicide rises in tandem with an increase in homicides in the general population ( Gottlieb et al., 1987 ; Gudjonsson and Petursson, 1986 ). A 40-year study based in the Chuvash Republic of the Russian Federation revealed that the rate of homicide associated with schizophrenia was significantly correlated with that in people without schizophrenia over this period ( Golenkov et al., 2021 ).

Conclusions

Our study showed that the incidences of violent offending in people with schizophrenia and those identified as NCRMD have been decreasing from 2010 to 2019 in Hunan Province, China. The incidences were found to be significantly correlated with the incidence of violent offending in the general population over this period. The increase in mental health resources and the developing economy may play important roles in reducing violent offending associated with schizophrenia. This indicates that the prevention of violent offending in people with schizophrenia involves not only providing enhanced mental health resources and reinforcing treatment measures, but also addressing factors influence general violent offending. Our findings may have critical implications for the prevention and management of violent offending in people with schizophrenia.

Abstract

Background. Because nightmares seem to be associated with depression in schizophrenia, detecting them early in therapeutic practice might be critical to ensuring effective avoidance of the development of depressive symptomatology. This helps promote well-being and improve the patient’s quality of life and illness prognosis. Therefore, the aim of this study was to examine the indirect effect of depression between nightmares and well-being in a Lebanese sample of patients with schizophrenia. Method. This monocentric cross-sectional study, conducted in July 2022, enrolled patients with chronic schizophrenia admitted to the Psychiatric Hospital of the Cross. Data were collected from a total of 148 participants through face-to-face interviews. The questionnaire included a nightmares measure, PSYRATS, Calgary depression scale for schizophrenia, PTSD checklist for DSM-5, the digit span subset, and WHO-5Well-Being Index. Results. The presence of nightmares was significantly associated with more depression, whereas higher depression was significantly associated with lower well-being. It is noteworthy that the presence of nightmares was not directly associated with well-being. Conclusion. Nightmares lead indirectly to lower well-being in schizophrenia patients, with depression serving as a mediating factor in this association. This suggests that interventions aiming at improving dream content may also have a beneficial effect in reducing depression in schizophrenia leading therefore to better well-being of the patients.

Background

Schizophrenia is one of the most severe mental disorders when it comes to its detrimental effects on various psychosocial areas and the overall quality of life of the patient [1]. Because schizophrenia causes misery and incapacity, the majority of attention has been focused on understanding and mitigating its negative effects on daily life functioning, with a rising focus on broad positive variables such as life satisfaction and subjective well-being [2]. Well-being has been widely acknowledged to entail both functioning effectively and feeling well [3]. Therefore, it is important to note that suffering from mental disorders does not imply poor well-being, and the lack of psychopathology does not guarantee a productive lifestyle [4]. Promoting well-being, on the other hand, can greatly aid recovery and improve the patient’s quality of life and illness prognosis [5]. Therefore, it is important to study factors that may affect the well-being of patients diagnosed with schizophrenia for better functioning and recovery. A variety of psychological and biological factors, such as long-term environmental influences and ongoing stressors, general cognitive abilities and personality traits, exposure to transiently traumatic life events, mental health interventions, and coping, affect the functioning and well-being of schizophrenia patients [6]. Trauma and posttraumatic stress disorder (PTSD), which are commonly prevalent among individuals with schizophrenia [7], are linked to personal well-being, which can be optimized following PTSD treatment [8]. However, the diagnosis of depression is likely the one most closely associated with a lack of well-being [4]. Patients with mental disorders, particularly those with schizophrenia, commonly experience depression [9]. Comorbid depressive symptoms, estimated in 30–75% of schizophrenia patients [10], have been linked to worse long-term functioning [11] and a lower level of life quality and well-being [12]. The World Health Organization has reported that schizophrenia is the fourth most prominent cause of disability globally [13]. Individuals with schizophrenia who also suffer from depression experience a substantial level of disability [14], which impairs their ability to manage their mental and physical health, leading to a vicious cycle of deteriorating disability [15]. Moreover, it has been discovered that depression plays a partial mediator role in the connection between the severity of schizophrenia and disability [16]. Given the magnitude of negative symptoms, the impairments in functioning and well-being, and the risk of suicidality, schizophrenia patients with depressive symptoms should be monitored closely [17]. This occurrence of depressive symptoms in schizophrenia may be caused by overlapping risk factors, thereby having an impact on these patients’ general well-being.

Conclusion

Our findings demonstrate that nightmares lead to lower well-being in schizophrenia patients, with depression serving as a mediating factor in this association. As a result, the outcomes of this research may represent a first step towards emphasizing the importance of addressing patients’ distressing dreams during therapy in order to alleviate their depressive symptoms, which in turn promotes improved well-being. We support further investigation into nightmares as a potential indirect causal component of decreased well-being in schizophrenia to improve the quality of life and general subjective well-being among schizophrenia patients.

Summary

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Introduction

Schizophrenia is a debilitating psychiatric disorder occurring in ∼0.3% of the global population with severe repercussions for patients, families, and society.1,2 The last years have seen great advances in mapping the genetic architecture of schizophrenia, identifying hundreds of common and rare variants that confer risk for the disorder across diverse populations.3,4,5,6,7,8,9,10 These studies also revealed overlapping genetic signals between schizophrenia, autism spectrum disorders (ASD), and severe developmental disorders (DD), supporting the importance of neurodevelopmental processes in the pathophysiology of schizophrenia.9,10,11 However, although the identified schizophrenia risk genes provide a good entry point for systematic studies of the disorder and its related conditions, their molecular functions and interactions in the brain remain poorly understood, hindering the development of effective treatments and therapeutics.12,13

In parallel, analyses of postmortem brains from individuals with schizophrenia and integration of genetic and transcriptomic data from human and mouse brains have converged on cortical excitatory neurons as a key biological conduit of genetically encoded risk.14,15,16,17 This suggests that systematic mapping of schizophrenia risk genes onto protein-protein interaction (PPI) networks in this cell type could reveal mechanisms and pathways underlying schizophrenia.18,19 A seminal study showed that adding extrinsic neuronal patterning to pluripotent stem cells (PSCs) overexpressing NGN2 generates glutamatergic induced neurons (iNs) that behave like cortical excitatory neurons at the molecular, morphological, and functional levels.20,21 Here, we leveraged this protocol to perform interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in a neuronal cell model. By integrating the resulting PPI networks with orthogonal datasets, we showed that our approach creates a unique opportunity to investigate the roles of schizophrenia risk genes and their associated pathways in a brain cell-type-specific context.

Results

Prioritization of schizophrenia index genes with shared neurodevelopmental signals
To identify schizophrenia risk genes as the basis of our interactome experiments we designed and executed a three-step procedure (Figure 1A and Table S1). First, we identified 445 genes (Set 1) in previously reported genome-wide significant loci from the Psychiatric Genomics Consortium (PGC) genome-wide association study3 (GWAS; phase 2). Second, we filtered this set to 37 genes (Set 2) within single protein-coding gene loci, excluding other genes in loci with more ambiguous association signals. Third, we integrated data from orthogonal studies (e.g., high-density genotyping, exome sequencing, and earlier targeted studies of individual genes; STAR Methods and Table S1) to identify a subset of 10 genes (Set 3) supported by multiple independent lines of evidence. Importantly, we used orthogonal evidence from rare variant studies of ASD/DD to prioritize schizophrenia risk genes that have also been implicated in neurodevelopmental conditions. We additionally included SYNGAP1 in the major histocompatibility complex (MHC) region in all three sets because of strong orthogonal evidence for its involvement in schizophrenia and neurodevelopmental disorders.

Abstract

     Some evidence suggests that patients with bipolar disorder (BD) have better Theory of Mind (ToM) skills than patients with schizophrenia/schizoaffective disorder (SCH). However, this difference is not consistently reported across studies, so rather than being global, it may be restricted to specific aspects of ToM. Our primary objective was to compare higher order ToM performance between BD and SCH patients using the Hinting Task (HT). Ninety-four remitted patients were recruited (BD = 47, SCH = 47). Intelligence quotient (IQ), attention, memory, executive functions, and processing speed were also assessed. Patients with BD performed better on the HT than patients with SCH, even when the analysis was adjusted for IQ and neurocognition (p < 0.001, η2p = 0.144). Regression analysis in the total sample showed that a diagnosis of SCH and lower IQ were associated with lower HT scores (R2 = 0.316, p < 0.001). In the BD group, verbal memory and processing speed were the main predictors of HT performance (R2 = 0.344, p < 0.001). In the SCH group, no variable was significant in explaining HT performance. In the context of previous studies that found no significant differences in the most basic aspects of ToM (e.g., understand other people’s thoughts/beliefs), our results suggest that differences between the two disorders might be limited to the more challenging aspects (e.g., understand the intended meaning of indirect requests). No causal inferences can be made in this cross-sectional study. However, regression analyses show that whereas in BD patients, ToM functioning would be partially modulated by neurocognitive performance, in SCH patients, it could be largely independent of the well-known neurocognitive impairment.

Introduction

     “Theory of Mind” (ToM) encompasses the ability to understand the cognitive and afective mental states of oneself and others and the ability to use this knowledge to predict and anticipate people’s behavior [1]. Patients with bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH) show mild-to-severe defcits in ToM throughout the course of the disease, including the prodromal, acute, and remitted phases [2, 3]. Although less severe, similar difculties have been observed in their unafected frst-degree relatives, suggesting some degree of heritability and that ToM difculties are a vulnerability marker for BD and SCH [4, 5].

     ToM is more closely related to social functioning than most clinical and neurocognitive variables. Therefore, an intact ToM is essential for adequate performance at work and in the community [6, 7]. However, it is not a monolithic function. Instead, it consists of several sub-processes among which the frst-order ToM (i.e., the ability to know what another person thinks or believes), the second-order ToM (i.e., the ability to know what a person thinks that another person thinks or believes) and other forms of higher order ToM (e.g., understand sarcasm, metaphors or indirect requests) stand out [8].

Conclusion

     Our results show that patients with BD perform signifcantly better on higher order ToM than patients with SCH, independent of group diferences in other neurocognitive domains, but that general intelligence infuences this difference. Contextualized in the current literature, the present fndings suggest that the diferences between the two disorders may be subtler than previously thought, mainly afecting the more complex and sophisticated aspects of ToM. As clinical implications, both groups of patients could beneft from rehabilitation interventions designed to improve cognitive functioning. However, whereas BD patients would beneft from rehabilitation of verbal memory and processing speed [61], in SCH patients, additional efort should be made to rehabilitate the more challenging aspects of ToM [62]. Our fndings also have practical implications for how we should communicate with patients with BD and, especially, SCH. Ambiguity, irony, and the use of double meanings are frequent sources of misunderstanding and should be avoided.

Abstract

     Introduction: Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may play a role in the development of depression and anxiety. Therefore, nutritional approaches are potential strategies for the treatment of BD. The aim of this review is to summarize the available evidence on nutrition and BD. Materials and Methods: The paper was developed based on PRISMA 2020 guidelines. The search was conducted in Sep-2021 using PubMed and Cochrane Library, augmented by manually checked references lists. The search found 986 studies, of which 47 were included, combined with 13 from reference lists, totaling 60 studies. Results: There were 33 observational trials, of which 15 focused on fatty acids, 9 on micronutrients, 5 on specific foods, 4 on macro and micronutrients. The 27 interventional studies mainly focused on fatty acids, micronutrients and N-acetylcysteine (NAC). Discussion: Dietary intake or supplementation of unsaturated fatty acids, mainly Omega-3 seems to be associated with improved BD symptoms, along with seafood, folic acid and zinc. Studies found variable, mainly non-significant impacts of creatine, carnitine, vitamin D, inositol or NAC supplementation on BD. There are promising results associated with Coenzyme Q10 (Coq10) and probiotics. Taken together, these preliminary findings suggest that dietetic approaches might be included as part of BD treatment. Also considering the high risk of metabolic disorders in individuals with BD, they should be encouraged to choose healthy dietary lifestyles, including daily intake of fruits, vegetables, seafood and whole grains.

Introduction

     Nutritional psychiatry is a rapidly expanding field of study, which has recently benefited from the advances of neurosciences, epidemiological research on risk factors as well as the renewed interest in the role of lifestyle in mental health [1]. Extensive observational evidence consistently demonstrates that diet quality is a predictor of depression risk – independent of other factors, such as education and body weight [2]. Moreover, randomized controlled trials in people with even severe major depressive disorder show efficacy and cost-effectiveness in improving depression symptomatology [3–7]. Concordantly, meta-analytic data confirms that dietary change improves depression symptoms in both clinical and non-clinical populations [8]. Considering that poor diet and dysfunctional eating behaviors are modifiable risk factors, it is possible that these will be converted into critical interventions for mental health [3,9,10]. Indeed, new clinical practice guidelines for mood disorders include diet, along with other aspects of lifestyle, as foundational and ‘non-negotiable’ treatment targets [1,11].

Results 

Search results

     The final search yielded 986 studies. After removing duplicates (N = 60), studies in other languages and publications prior to 2001 (N = 97), titles and abstracts from 829 studies were screened. Studies that did not clearly meet the inclusion criteria and/or met the exclusion criteria were excluded. The remaining 57 studies were analyzed by full text reading, after which 10 were excluded because they did not meet the full inclusion criteria. This led to 47 included studies, which were combined with 13 studies that were obtained from the bibliography from the included studies and reviews found in the search, totaling 60 studies (Figure 1).

Abstract

1. Introduction

2. Methods

3. Results

4. Discussion

Funding statement

References

Abstract

Background
     A challenge for clinicians working with individuals diagnosed with schizophrenia is distinguishing depressive symptoms from negative symptoms of schizophrenia. The Calgary Depression Scale for Schizophrenia (CDSS) was developed for this purpose. No review has previously explored its reliability across multiple studies using advanced statistical means.

Objectives
     This meta-analysis aimed to quantify the CDSS’ internal consistency, inter-rater reliability (IRR) and test-retest reliability.

Method
     A systematic literature search was conducted to find articles reporting on the CDSS’ reliability. Articles were screened against the inclusion and exclusion criteria, with data extracted from 40 studies. Overall meta-analytic effects were calculated, and for internal consistency and IRR coefficients subsequent analyses explored between-study variation. The small test-retest reliability dataset limited analysis.

Findings
     The internal consistency meta-analytic effect was 0.83 (95% CI:0.82–0.84). Higgins I2 indicated an acceptable level of variation between studies’ alpha estimates. This suggests all items in the CDSS are measuring the same construct (i.e. symptoms of depression). The IRR meta-analytic effect was 0.88 (95% CI:0.86–0.91), with Higgins I2 indicating high levels of heterogeneity. This was not deemed problematic variance as it is within levels expected for psychometric measures and, therefore, considered acceptable for this literature. This reflects high level of agreement between different raters when using the CDSS on the same client.

Conclusions
     This review suggests the CDSS has good internal consistency and excellent IRR. Further research will help understand its test-retest reliability.

Introduction

     Schizophrenia is associated with a range of symptoms, typically separated into positive and negative. Positive symptoms are associated with the individual’s perception or interpretation of stimuli being different from others, alongside difficulties distinguishing their thoughts and ideas from reality. Negative symptoms include loss of motivation, apathy, impaired concentration, flattening of emotions and reduced speech (Cuesta et al., 2009).

     It is widely accepted that mood disturbances are often observed alongside a diagnosis of schizophrenia (Rector et al., 2005; van Os et al., 2000). This includes mood disturbances experienced concurrently and independently from the psychotic symptoms (Birchwood et al., 2000). Negative symptoms, however, overlap with symptoms of depression, posing a clinical challenge of distinguishing negative symptoms of schizophrenia (i.e. difficulties with motivational state) from depression (i.e. difficulties with pervasive low mood).

Results

     Results 3.1. Study characteristics Table 2 presents the characteristics of the 39 studies included in the meta-analysis. Of the 40 studies, 27 were included for the CDSS’ internal consistency and 28 were included for the IRR of the CDSS. Eight of these studies also reported test-retest reliability data, however, due to limitations within this dataset the analysis was restricted (further information in Sections 3 and 4).

3.2. Risk of bias of individual studies Findings of meta-analyses can be impacted by including poor quality studies (Higgins et al., 2011). Quality captures how appropriate the study is for answering its research question, considering design, delivery and analysis. There are various tools for assessing risk of bias. Higgins et al. (2011) advocate using a set of criteria specific to methodological issues pertinent to the literature and question under review. Assessment of risk of bias, therefore, was completed using a framework developed for this review (Table 3). Existing tools and information on types of bias guided the framework’s development (Higgins et al., 2011; Smith and Noble, 2014).

Risk of bias ratings were primarily made by the lead author (LP), who also completed the process of data extraction. When there was ambiguity within the data which complicated the decision as to whether there was a low, unclear or high risk of bias, a discussion was had between the authors (LP, CJ and AF) to enable the final decision to be made by consensus.

Abstract

Keywords

1. Introduction

2. Methods

3. Results

4. Discussion

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgements

References

Abstract

Background
Previous research has reported that patients with schizophrenia would regard false memories with higher confidence, and this meta-memory deficit was suggested as a neurocognitive marker of schizophrenia. However, how schizophrenia patients determine their memory decision confidence has received scant consideration. This study, therefore, aimed to characterize the extent to which meta-memory evaluation strategy differs between schizophrenia patients and healthy individuals, and how such difference contributes to the patients’ meta-memory performance.

Methods
27 schizophrenia patients and 28 matched healthy controls performed a temporal-order judgement (TOJ) task, in which they judged which movie frame occurred earlier in an encoded video, and then made retrospective confidence rating. Mixed effect regression models were performed to assess the between-group metacognitive evaluation strategy difference and its relationship to clinical symptoms.

Results
Compared to the control group, the patients’ confidence ratings were correlated more with the recent confidence history and less with the TOJ-related evidence. The degree of dependence on recent history of confidence was negatively correlated with the severity of positive symptoms. Furthermore, by controlling for the first-order TOJ performance, we observed that the patients discriminated correct memory decisions from the incorrect ones as accurately as the controls.

Conclusion
The present investigation revealed that schizophrenia patients tend to use more heuristics in making meta-memory evaluations, and such atypical strategy is related to their clinical symptoms. This study provides new insights into how schizophrenia patients perform meta-memory processes. Future research could consider examining such metacognitive deficits in light of other cognitive domains in psychosis.

abstract

1. Introduction

2. Methods and materials

3. Results

4. Discussion

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgements

References

Abstract

 Objective
Altered interhemispheric connectivity is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD) and may account for deficits in lateralized cognitive processes. We measured transcranial magnetic stimulation evoked interhemispheric signal propagation (ISP), a non-invasive measure of transcallosal connectivity, and hypothesized that the SCZ and MDD groups will have increased ISP compared to healthy controls.

Methods
We evaluated ISP over the dorsolateral prefrontal cortex in 34 patients with SCZ and 34 patients with MDD compared to 32 age and sex-matched healthy controls.

Results
ISP was significantly increased in patients with SCZ and patients with MDD compared to healthy controls but did not differ between patient groups. There were no effects of antidepressant, antipsychotic, and benzodiazepine medications on ISP and our results remained unchanged after re-analysis with a region of interest method.

Conclusion
Altered ISP was found in both SCZ and MDD patient groups. This indicates that disruptions of interhemispheric signaling processes can be indexed with ISP across psychiatric populations.

Significance
These findings enhance our knowledge of the physiological mechanisms of interhemispheric imbalances in SCZ and MDD, which may serve as potential treatment targets in future patients.

Introduction

     Interhemispheric functional asymmetry is disrupted in psychiatric disorders such as schizophrenia (SCZ) and major depressive disorder (MDD) (Garcia-Toro et al., 2001, Ribolsi et al., 2009). In SCZ, deficits of lateralized sensorimotor and cognitive processes are linked to impaired cerebral specialization and interhemispheric communication (David, 1994, Whitford et al., 2010), in accordance with the disconnection hypothesis (Friston, 1999). Meanwhile, patients with MDD typically present with deficits in mood, emotion, and cognitive processing which also rely on hemispheric lateralization (Davidson, 2002). The corpus callosum is the largest white matter connective pathway in the brain and plays a critical role in interhemispheric connectivity, particularly for the lateralization of cognitive and perceptual processes (Gazzaniga, 2000). Transcallosal connectivity relies on a complex interplay of excitatory and inhibitory processes involving glutamate release from callosal axon terminals (Kawaguchi, 1992) and GABAergic neurotransmission initiated by local inhibitory interneurons in the contralateral hemisphere. Functional impairments of lateralized processes may reflect an underlying imbalance between excitatory and inhibitory signaling processes in the two hemispheres.

Results

3.1. ISP

     The ANOVA yielded a significant effect of group on ISP (F (2,97) = 7.24, p = 0.001). Post-hoc t-test comparisons revealed increased ISP in SCZ patients than in healthy controls (t(64) = – 3.642, p = 0.002; Bonferroni corrected p < 0.05; d’ = 0.90) and in MDD patients compared to healthy controls (t(64) = -3.311, p = 0.01; Bonferroni corrected p < 0.05; d’ = 0.82) (Fig. 1). We found no differences in ISP between SCZ patients and MDD patients (t(66) = -0.545, p = 1.00, d’ = 0.13) (Fig. 1). The group mean topoplots and rectified TEPs are shown in Fig. 2. To evaluate whether elevated ISP was also extended to remote regions, we measured ISP in the T7 and T8 regions and found no significant differences between groups (F(2,97) = 0.20, p = 0.82).

3.2. Correlation with symptom severity

     There was a trending correlation between ISP values and the HRSD scores for patients with MDD (r = 0.334, p = 0.054), suggesting that increased depression severity may be related to higher levels of signal transmission to the unstimulated hemisphere. For patients with SCZ, the total BPRS score and summed factor BPRS were used to determine the relationship between clinical severity with ISP. There was no correlation between ISP values with the total BPRS score (r = -0.005, p = 0.979), affective symptoms (r = 0.255, p = 0.145), psychotic symptoms (r =

Introduction: Comorbid depressive symptoms (depression thereafter) often occur in schizophrenia and are associated with negative outcomes. This meta-analysis estimated the prevalence of comorbid depression and its associated factors in schizophrenia. Methods: Both international (PubMed, EMBASE, PsycINFO, and Web of Science) and Chinese (WANFANG and CNKI) databases were systematically searched. Studies with data on the prevalence of comorbid depression in schizophrenia measured with the Calgary Depression Scale for Schizophrenia (CDSS) were included. Randomeffects models were used in all analyses. Results: Fifty-three studies covering 9,879 patients were included. The pooled prevalence of comorbid depression was 28.6% (95%CI: 25.3%-32.2%). Subgroup analyses revealed that studies examining inpatients, being published in Chinese language, or those with lower CDSS cut-od values reported higher depression rates. Metaregression analyses indicated that the rate of depression was positively associated with publication year, proportion of males, mean age, and severity of psychotic symptoms, and negatively associated with illness duration and study quality. Conclusion: Comorbid depression is common in schizophrenia. Due to its negative impact on patients’ quality of life and prognosis, regular screening and effective treatment for comorbid depression should be implemented in patients with schizophrenia.

Introduction

Comorbid depressive symptoms (depression thereafter) are present in all phases of schizophrenia (Naguy, 2018; Upthegrove, 2009) and correlated with higher risk of suicide (Ayesa-Arriola et al., 2015; Bagaric et al., 2013; Li et al., 2018), polypharmacy (Lako et al., 2012b), worse psychosocial functioning (Schennach‐Wolff et al., 2011), and poorer quality of life (Alessandrini et al., 2016; Sim et al., 2004), and functional outcomes (Conley et al., 2007). Because comorbid depression is often under-diagnosed in schizophrenia, patients may not receive appropriate treatment (Lako et al., 2012b; Majadas et al., 2012; Upthegrove et al., 2017). Elucidating the pattern of comorbid depression and its correlates in schizophrenia could benefit the management and prognosis of affected patients. The prevalence of comorbid depression varies greatly across studies; for instance, one study (Dai et al., 2018) found the rate of depression measured with the 17-item Hamilton Depression Rating Scale (HAMD-17) in schizophrenia inpatients was 54.6%, while the corresponding figures were 12.9% when using the Present State Examination (PSE) (Barnes et al., 1989) and 31% in outpatients with the Calgary Depression Scale for Schizophrenia (CDSS) (Majadas et al., 2012). Discrepancies between these studies could be partially due to different study settings, the severity of psychotic symptoms, and assessment instruments. Several scales have been used to assess comorbid depression in schizophrenia including generic ones, such as the HAMD and PSE, that have not been validated in schizophrenia and they are not as sensitive as schizophrenia-specific measures, such as the CDSS. The 9-item CDSS was developed to identify comorbid depression in schizophrenia; its total score ranges from 9 to 27 with a higher total score indicating more severe depression. The CDSS has satisfactory psychometric properties and has been widely used (Lako et al., 2012a; Scholes and Martin, 2013). Different CDSS cutoff values have been applied in research and clinical practice: a total score of ≥5 (Hani et al., 2016), ≥6 (Chang et al., 2015), ≥7 (Fountoulakis et al., 2017), >7 (Thomas et al., 2014), or ≥12 (Üçok et al., 2013).

1- Introduction

2- Methods

3- Results

4- Discussion

5- Conclusion

References

Abstract

Suicide risk in schizophrenia is a significant treatment challenge but there are few approved treatments. Electroconvulsive therapy (ECT) is a highly effective treatment for suicidality in depression but its effect on suicidality in schizophrenia is unclear. We conducted a retrospective naturalistic study of the real-world effect of ECT on expressed suicidality as assessed by item 4 of the 24-item Brief Psychiatric Rating Scale in 113 patients with treatment resistant schizophrenia receiving ECT. 19.5% of patients expressed suicidal ideation pre-ECT of which 86.4% experienced an improvement in expressed suicidality after an average of 10.2 (SD 2.7) sessions of ECT. Changes in suicide scores before and after ECT was examined using a generalized estimating equation (GEE) model which showed that the effect of ECT on suicide was significantly mediated by depression and explained 72.2% of the decreased in expressed suicidality. ECT is effective in decreasing depression and expressed suicidality in patients with schizophrenia and should be considered as a treatment option for managing suicidality and psychosis in patients with treatment resistant schizophrenia.

Introduction

Schizophrenia is a chronic severe mental illness with premature mortality that is partially accounted for by increased suicides (Palmer et al., 2005). The lifetime risk of suicide in schizophrenia is estimated to be as high as 13% (Drake et al., 1985) and 8.5 fold that of the general population (Harris and Barraclough, 1997). Despite this high risk of suicide, there are few approved treatments to address suicidality in schizophrenia (Kasckow et al., 2011). Only clozapine is US FDA approved to treat suicidality in schizophrenia (Meltzer et al., 2003) and SSRIs may be helpful to decrease suicidality in schizophrenia (Zisook et al., 2010). Electroconvulsive therapy (ECT) is the oldest somatic treatment modality in psychiatry still in current use (Cerletti and Bini, 1938). It is the most effective acute treatment for severe depression (Carney et al., 2003) and also effective in reducing psychotic symptoms in treatment resistant schizophrenia (American Psychiatric Association, 2008; Petrides et al., 2014; Tharyan and Adams, 2005). ECT is highly effective in rapidly decreasing suicidality in depression (Fink et al., 2014; Kellner et al., 2005; Prudic and Sackeim, 1999) and can be life saving for some patients. However, the effect of ECT on suicidality in schizophrenia is unclear. We thus set out to investigate the effect of ECT on expressed suicidality in schizophrenia in a large naturalistic cohort of patients with treatment resistant schizophrenia receiving ECT. Singapore is a small nation state at the tip of the Malaysian archipelago. It has a population of approximately 5.5 million people consisting of 74.3% ethnic Chinese, 13.3% Malays and 9.1% Indian (Department of Statistics Singapore, 2016). The Singapore Institute of Mental Health (IMH) is the only tertiary psychiatric hospital in Singapore and has 1900 inpatient beds and about 40,000 outpatients. The IMH treats about 80% of the national load of patients with schizophrenia. At the IMH, ECT is prescribed primarily for schizophrenia (47%) with schizoaffective disorder (20.3%), depression (20.4%) and mania (6.8%) being the other major indications. ECT was effective in treating psychotic symptoms in 64.5% of patients with schizophrenia and also improved cognitive functioning in these patients (Tor et al., 2017).