Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect.

(1) Background: Childhood-onset schizophrenia (COS) is a rare type of psychotic disorder characterized by delusions, hallucinations, grossly disorganized behavior, and poor psychosocial functioning. The etiology of COS is unknown, but neurodevelopmental factors are likely to play a critical role. A potential neurodevelopmental anomaly marker is the dorsal visual system dysfunction, which is implicated in motion perception, spatial functions, and attention. (2) Methods: To elucidate the role of the dorsal visual system in COS, we investigated 21 patients with COS and 21 control participants matched for age, sex, education, IQ, and parental socioeconomic status. Participants completed a motion and form coherence task, during which one assesses an individual's ability to detect the direction of motion within a field of moving elements or dots and to recognize a meaningful form or object from a set of fragmented or disconnected visual elements, respectively. (3) Results: The patients with COS were impaired in both visual tasks compared to the control participants, but the evidence for the deficit was more substantial for motion perception than for form perception (form: BF10 = 27.22; motion: BF10 = 6.97 × 106). (4) Conclusions: These results highlight the importance of dorsal visual stream vulnerability in COS, a potential marker of neurodevelopmental anomalies.

We report two cases of paternally inherited 15q13.3 duplications in carriers diagnosed with childhood-onset schizophrenia (COS), a rare neurodevelopmental disorder of proposed polygenic origin with onset in children before age 13. This study documents that the 15q13.3 deletion and duplication exhibit pathogenicity for COS, with both copy number variants (CNVs) sharing a disrupted CHRNA7 gene. CHRNA7 encodes the neuronal alpha7 nicotinic acetylcholine receptor (α7nAChR) and is a candidate gene that has been suggested as a pathophysiological process mediating adult-onset schizophrenia (AOS) and other neurodevelopmental disorders. These results support the incomplete penetrance and variable expressivity of this CNV and represent the first report of 15q13.3 duplication carriers exhibiting COS. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc.

Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes.

Childhood trauma has been linked to schizophrenia, but underlying biological mechanisms remain elusive. This study explored the potential role of plasma oxytocin as a mediator in the relationship between childhood trauma and the psychopathology of schizophrenia. 160 patients with schizophrenia and 80 age- and sex-matched healthy controls were assessed for childhood trauma experiences using the Childhood Trauma Questionnaire and structured interviews. Psychopathology was evaluated using the Positive and Negative Syndrome Scale and plasma oxytocin levels were measured. Results showed that patients with schizophrenia had lower oxytocin levels and higher childhood trauma scores than healthy controls. There was a significant correlation between childhood trauma scores and psychopathology, with plasma oxytocin levels being inversely associated with psychopathology, except for positive symptoms. Hierarchical regression analysis indicated that both childhood trauma scores and plasma oxytocin levels significantly predicted psychopathology. Plasma oxytocin levels partially mediated the relationship between childhood trauma and schizophrenia psychopathology. This study underscores the potential role of oxytocin in bridging the gap between childhood trauma and schizophrenia.

We describe a child with onset of command auditory hallucinations and behavioral regression at 6 yr of age in the context of longer standing selective mutism, aggression, and mild motor delays. His genetic evaluation included chromosomal microarray analysis and whole-exome sequencing. Sequencing revealed a previously unreported heterozygous de novo mutation c.385G>A in ATP1A3, predicted to result in a p.V129M amino acid change. This gene codes for a neuron-specific isoform of the catalytic α-subunit of the ATP-dependent transmembrane sodium-potassium pump. Heterozygous mutations in this gene have been reported as causing both sporadic and inherited forms of alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism. We discuss the literature on phenotypes associated with known variants in ATP1A3, examine past functional studies of the role of ATP1A3 in neuronal function, and describe a novel clinical presentation associated with mutation of this gene.

Childhood trauma is a risk factor for psychosis as well for violent behavior and offending later in life. Childhood trauma comprises subdomains of abuse and neglect that may be differently related to later violence among patients with schizophrenia. The aim of this study was to map the subdomains of childhood trauma associated with violent offending in schizophrenia.

Schizophrenia is a highly heritable psychiatric disorder, and recent studies have suggested that exposure to nitrogen dioxide (NO2) during childhood is associated with an elevated risk of subsequently developing schizophrenia. However, it is not known whether the increased risk associated with NO2 exposure is owing to a greater genetic liability among those exposed to highest NO2 levels.

There is recent evidence of some degree of shared genetic susceptibility between adult schizophrenia and childhood attention-deficit hyperactivity disorder (ADHD) for rare chromosomal variants.

Background: Sexual hallucinations are probably the most neglected types of hallucination, even in psychiatric settings. They are often multimodal in nature, and their prevalence rate is unknown. For other types of hallucination, notably auditory hallucinations, childhood trauma is an important risk factor. However, whether this also applies to sexual hallucinations is unexplored. Objective: To establish the prevalence rate of sexual hallucinations in a clinical sample of patients diagnosed with a schizophrenia spectrum disorder, to describe their phenomenological characteristics, and to estimate their relationship with childhood trauma. Methods: After screening 778 patients diagnosed with a schizophrenia spectrum disorder, 42 were considered eligible for inclusion by their treating physician or psychiatrist. Thirty of these patients were interviewed to assess the presence of sexual hallucinations, using a tailor-made questionnaire and the short form of the Childhood Trauma Questionnaire. Results: Of the 30 patients interviewed, 13 reported sexual hallucinations, yielding a 1-year prevalence rate of 0.017 in this clinical sample. Of the hallucinating patients, 46.2% reported multimodal hallucinations, with involvement of up to five sensory modalities. All patients who experienced sexual hallucinations reported a history of childhood trauma, of which 76.9% involved sexual trauma (OR 8.7). In addition, 61.5% of the patients reported high levels of distress. Conclusion: In patients diagnosed with a schizophrenia spectrum disorder, sexual hallucinations warrant appropriate medical attention. They are not as rare as traditionally thought, and their relationship with childhood trauma is overwhelming. Therefore, we recommend that clinical attention be paid to the psychotic and traumatic symptoms of these patients, as well as to the somatic conditions that may underlie them. For clinical and research purposes, we propose a classification of sexual hallucinations in accordance with the sensory modalities involved. As sexual hallucinations are also experienced in the context of temporal lobe epilepsy, narcolepsy, persistent genital arousal disorder, intoxications and other somatic conditions, further research in transdiagnostic populations seems warranted. In line with the current practice of providing trauma-focused treatment for trauma-related auditory hallucinations, we recommend that future studies explore the effectiveness of this type of treatment for sexual hallucinations.

There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene-environment correlation.

Schizophrenia is believed to be etiologically associated with environmental factors. Poor parental bonding, especially arising from "low care" and "overprotection," may contribute to the prognosis in patients with psychosis. In the present study, we investigated the associations between the aforementioned two different parental bonding types and the prognosis, in terms of the functional recovery, of patients with schizophrenia.

Modularity is a fundamental concept in systems neuroscience, referring to the formation of local cliques or modules of densely intra-connected nodes that are sparsely inter-connected with nodes in other modules. Topological modularity of brain functional networks can quantify theoretically anticipated abnormality of brain network community structure - so-called dysmodularity - in developmental disorders such as childhood-onset schizophrenia (COS). We used graph theory to investigate topology of networks derived from resting-state fMRI data on 13 COS patients and 19 healthy volunteers. We measured functional connectivity between each pair of 100 regional nodes, focusing on wavelet correlation in the frequency interval 0.05-0.1 Hz, then applied global and local thresholding rules to construct graphs from each individual association matrix over the full range of possible connection densities. We show how local thresholding based on the minimum spanning tree facilitates group comparisons of networks by forcing the connectedness of sparse graphs. Threshold-dependent graph theoretical results are compatible with the results of a k-means unsupervised learning algorithm and a multi-resolution (spin glass) approach to modularity, both of which also find community structure but do not require thresholding of the association matrix. In general modularity of brain functional networks was significantly reduced in COS, due to a relatively reduced density of intra-modular connections between neighboring regions. Other network measures of local organization such as clustering were also decreased, while complementary measures of global efficiency and robustness were increased, in the COS group. The group differences in complex network properties were mirrored by differences in simpler statistical properties of the data, such as the variability of the global time series and the internal homogeneity of the time series within anatomical regions of interest.

Recent evidence shows that genetic and environmental risk factors for psychotic disorders are associated with higher levels of schizotypy (or psychosis proneness) in the general population. However, little is known about how these risk factors interact. We specifically examined whether genetic loading for schizophrenia moderates the association between childhood trauma severity and schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and childhood trauma severity was measured with the Childhood Trauma Questionnaire (CTQ) among a total of 168 participants (comprising 51 healthy individuals, 56 diagnosed with schizophrenia, and 61 with bipolar disorder). Polygenic risk scores (PRS) for schizophrenia were calculated for all participants and examined as a potential moderator of associations between total scores on the CTQ and schizotypy total scores and dimensions (i.e., cognitive-perceptual, interpersonal, disorganised). Multiple linear regression models revealed associations between childhood trauma and all dimensions of schizotypy, but no associations between PRS and schizotypy. A significant interaction between PRS and childhood trauma was evident for the interpersonal and disorganised dimensions of schizotypy, as well as the total score, reflecting positive associations between childhood trauma severity and these two schizotypal dimensions, only for individuals with low or average PRS for schizophrenia. This suggests that trauma may be able to increase risk for psychosis independently of any genetic vulnerability. The present findings are consistent with the idea of several risk pathways for the development of psychotic disorders.

A small percentage of all cases of schizophrenia have a childhood onset. The impact on the individual and family can be devastating. We report the results of genetic analyses from a patient with onset of visual hallucinations at 5 years, and a subsequent diagnosis at 9 years of schizophrenia, attention deficit hyperactivity disorder (ADHD) with hyperactivity and impulsivity, and chronic motor tic disorder.

Schizophrenia has been robustly associated with multiple genetic and environmental risk factors. Childhood adversity is one of the most widely replicated environmental risk factors for schizophrenia, but it is unclear if schizophrenia genetic risk alleles contribute to this association.

Approximately 5% of patients with schizophrenia commit suicide, and 20% to 40% of them have at least one suicide attempt during their lifetime. Previous research has identified childhood trauma as a potential risk factor for suicide attempt in schizophrenia. The Psychiatric Genetics Consortium found 108 common genetic risk loci associated with schizophrenia. Moreover, familial, adoption, and twin studies suggested that suicidal behaviour is under genetic influence.

Objectives: This study aimed to investigate the effect of childhood trauma, especially its specific dimensions, and clinical risk factors for suicidal ideation in patients with schizophrenia. Methods: A total of 83 inpatients with schizophrenia were enrolled and divided into two groups: with suicidal ideation (n = 33) and without suicidal ideation (n = 50). All participants were administered the Childhood Trauma Questionnaire-Short Form, the Insomnia Severity Index, the Beck Scale for Suicide Ideation, the Modified Overt Aggression Scales, the auditory hallucination rating scale, the Hamilton Rating Scale of Depression and the Positive and Negative Syndrome Scale. Results: In our sample, 39.8% of the subjects had suicidal ideation, and 60.6% of them had suffered from childhood trauma. Patients with suicidal ideation had a higher Insomnia Severity Index score, Physical neglect score, the Childhood Trauma Questionnaire-Short Form total score (all P < 0.05) compared to those without. The logistic regression analysis revealed that physical neglect in Childhood Trauma Questionnaire was significantly associated with suicidal ideation (OR = 5.46, P < 0.05, 95% CI = 0.007-0.483). Further stepwise multiple linear regression identified that insomnia (β = 0.272, P = 0.011) and physical neglect (β = 0.257, P = 0.017) were strong risk factors for the severity of suicidal ideation in patients with schizophrenia. Mediation analysis showed that insomnia played a complete mediating role between physical neglect and suicidal ideation. Conclusion: Our results indicate that childhood maltreatment of physical neglect is a strong independent risk factor for suicidal ideation in schizophrenia. The risk is probably aggravated by the poor quality of sleep. Early screening and psychosocial treatment are recommended for psychotic individuals with a trauma history.

Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS.

Childhood trauma, and in particular physical neglect, has been repeatedly associated with lower performance on measures of social cognition (e.g. emotion recognition tasks) in both psychiatric and non-clinical populations. The neural mechanisms underpinning this association have remained unclear. Here, we investigated whether volumetric changes in three stress-sensitive regions-the amygdala, hippocampus and anterior cingulate cortex (ACC)-mediate the association between childhood trauma and emotion recognition in a healthy participant sample (N = 112) and a clinical sample of patients with schizophrenia (N = 46). Direct effects of childhood trauma, specifically physical neglect, on Emotion Recognition Task were observed in the whole sample. In healthy participants, reduced total and left ACC volumes were observed to fully mediate the association between both physical neglect and total childhood trauma score, and emotion recognition. No mediating effects of the hippocampus and amygdala volumes were observed for either group. These results suggest that reduced ACC volume may represent part of the mechanism by which early life adversity results in poorer social cognitive function. Confirmation of the causal basis of this association would highlight the importance of resilience-building interventions to mitigate the detrimental effects of childhood trauma on brain structure and function.