Multisensory integration underlying body-ownership experiences in schizophrenia and offspring of patients: a study using the rubber hand illusion paradigm

Background: Schizophrenia is a disorder of basic self-disturbance. Evidence suggests that people with schizophrenia may have aberrant experiences of body ownership: they may feel that they are not the subject of their own body experiences. However, little is known about the development of such disturbances. Methods: Using a rubber hand illusion paradigm, we assessed body ownership in patients with schizophrenia (n = 54), healthy controls (n = 56), children/adolescents at increased familial risk of developing schizophrenia (n = 24) or mood disorders (n = 33), and children/adolescents without this risk (n = 18). In this paradigm, a rubber hand (visible) and a participant's real hand (invisible) were stroked synchronously and asynchronously; we then measured subjective illusory experiences and proprioceptive drift. Results: All groups showed the expected effect of the rubber hand illusion: stronger proprioceptive drift and increased subjective illusory experiences after synchronous versus asynchronous stroking. The effect of synchronicity on subjective experiences was significantly weaker in patients with schizophrenia than in healthy controls, and subjective ratings were positively correlated with delusions in patients. We found no significant differences between children/adolescents with and without increased familial risk. Limitations: Large individual differences raised questions for future research. Conclusion: We found subtle disturbances in body-ownership experiences in patients with schizophrenia, which were associated with delusions. We found no evidence for impairments in children/adolescents at increased familial risk of developing schizophrenia or a mood disorder. Longitudinal data might reveal whether impairments in body ownership are predictive of psychosis onset.

Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.

OBJECTIVES: There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder. METHODS: Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1ß (IL-1ß), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls. RESULTS: During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages. CONCLUSIONS: This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value.

Relationship between clinical features and inflammation-related monocyte gene expression in bipolar disorder - towards a better understanding of psychoimmunological interactions.

OBJECTIVES: Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro-inflammatory gene expression in patients with bipolar disorder (BD). We hypothesized a priori that increased monocyte pro-inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms. METHODS: Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro-inflammatory gene expression and clinical features, from which feature-expression heat maps were drawn. RESULTS: No associations were found between pro-inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti-epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression. CONCLUSIONS: Our hypothesis that lifetime psychotic features would be associated with pro-inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro-inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood-regulating medications.

Real-time personalized feedback in mHealth for adolescents.

Mobile Health (mHealth) interventions have the potential to improve early identification, prevention, and treatment of mental health problems. Grow It! is a multiplayer smartphone app designed for youth aged 12-25, allowing them to monitor their emotions and engage in daily challenges based on Cognitive Behavioral Therapy (CBT) principles. Recently, a personalized mood profile was added to improve the app. We investigated whether real-time personalized feedback on mood enhances app engagement, user experience, and the effects on affective and cognitive well-being. Sample A (N = 1269, age = 18.60 SD = 3.39, 80.6% girls, 95.4% Dutch) played the original app without feedback on their mood, and an independent Sample B (N = 386, age = 16.04 SD = 3.21, 67.6% girls, 82.9% Dutch) received the renewed version with personalized real-time feedback on their mood. Participants who received personal feedback did not have higher app engagement (t(1750,400) = 1.39, P = .206, d = 0.07; t(692,905) = 0.36, P = .971, d = 0.0) nor higher user experience (t(177,596) = 0.21, P = .831, d = 0.02; (t(794) = 1.28, P = .202, d = 0.12; χ2 (659,141) = 2.83, P = .091). Players of the renewed version (Sample B) experienced significant improvements in affective (t(175) = 3.01, P = .003, d = 0.23) and cognitive well-being (t(175) = 3.48, P = <.001, d = 0.26) over the course of three weeks. The renewed version Grow It! has the potential to enhance youths' affective and cognitive well-being. However, adding real-time insights did not seem to affect app engagement nor user experience.

Associations between autism traits and family functioning over time in autistic and non-autistic children.

LAY ABSTRACT: Little is known about family functioning over time when raising a child with autism traits, with or without a clinical autism diagnosis. Therefore, we asked caregivers-mostly parents-of a group of 168 children about the family functioning and the child's emotional and behavioral characteristics, as well as autistic traits, twice with about 1 year in between. For numerous reasons, the children were referred to youth mental health care centers, including child and adolescent psychiatric services. Care as usual was offered after the diagnostic assessment if a clinical diagnosis was the assessment outcome. Caregivers reported less problematic family functioning in children with fewer autism traits over time. The child's additional emotional or behavioral characteristics did not seem to influence this relation. Furthermore, we split the whole group into autistic children with a clinical autism diagnosis (58%) and non-autistic children with autism traits but without a clinical diagnosis (42%) to see whether we would find the same results in both groups. Surprisingly, the relation between family functioning and the level of a child's autism traits only held for the subgroup of non-autistic children with autism traits. Thus, raising children with autism traits without a clinical diagnosis may affect family functioning over time. We think that families might have difficulty understanding and adjusting to the autism traits of their children but are lacking the support that is exclusively offered to families of children with a clinical autism diagnosis. We must be cautious because we do not know whether there is a causal relation. Although further research is needed to explore and learn to understand this result, clinicians might consider offering support to families of children with subthreshold autism to prevent problems in family functioning. Because high autism trait levels in non-autistic children may be of a different origin than autism, for example, other neurodevelopmental or mental health problems, family training or support should be tailored to the child's underlying difficulties.

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients.

Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

The influence of life events on first and recurrent admissions in bipolar disorder.

BACKGROUND: Life events play an important role in the onset and course of bipolar disorder. We will test the influence of life events on first and recurrent admissions in bipolar disorder and their interaction to test the kindling hypothesis. METHODS: We collected information about life events and admissions across the life span in 51 bipolar patients. We constructed four models to explore the decay of life event effects on admissions. To test their interaction, we used the Andersen-Gill model. RESULTS: The relationship between life events and admissions was best described with a model in which the effects of life events gradually decayed by 25% per year. Both life event load and recurrent admissions significantly increased the risk of both first and subsequent admissions. No significant interaction between life event load and number of admissions was found. CONCLUSIONS: Life events increase the risk of both first and recurrent admissions in bipolar disorder. We found no significant interaction between life events and admissions, but the effect of life events on admissions decreases after the first admission which is in line with the kindling hypothesis.

Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents.

OBJECTIVE: For nearly 5 years a prospective high risk cohort study was carried out in the Netherlands among adolescent offspring of parents with bipolar disorder (BD). The purpose of this study was to determine the prevalence of psychopathology, specifically mood disorders, in adolescents and young adults with a bipolar parent. METHOD: At first and second measurement 140 and 132 children of bipolar parents, respectively, were psychiatrically evaluated with a semi-structured psychiatric interview (K-SADS-PL). At follow up (third measurement), nearly 5 years later, lifetime DSM IV diagnoses were obtained from the SCID interview for 129 subjects (aged 16--26 years). RESULTS: Compared with the first measurement, the lifetime prevalence of BD increased from 3 to 10% at follow up. In addition, the lifetime prevalence of overall mood disorders increased to 40% and of overall psychopathology to 59%. All subjects except for one with BD, debuted with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to the first (hypo)manic episode. CONCLUSION: At follow up, we noticed an increase in BD onset, while a further increase could be expected. In addition, we found that a unipolar depression in bipolar offspring is a risk factor for, and at the same time the first sign of, the development of BD.