Ten years of infant mental health in the Netherlands:Who are the clients?

Background: Infant Mental Health (IMH) is a topic of current interest that emerged over the past decades, concerned with alleviating suffering and enhancing the social and emotional competence of young children. Worldwide there is increasing recognition of infant psychopathology meriting intervention. However, there are still limited data regarding the prevalence of psychiatric disorders and sociodemographic characteristics of these youngest of patients in clinical settings. Aim: This large, descriptive study aims at presenting the socio-demographic and clinical characteristics of infants referred consecutively to three outpatient Infant Mental Health teams in the Netherlands between September 2000 and July 2013. Methods: The medical records of 783 infants were retrospectively examined and the data were collected from paper and electronic patient files. Clinical and socio-demographic characteristics were categorized in child factors, developmental milestones, family factors and clinical outcome measures (DSM-IV, DC:0-3R, WIPPSI-III, SON-R 2½-7). Results: Our sample showed significantly more boys (543, 69%) than girls (240, 31%) being referred to the Infant Mental Health teams. Most children were referred when they were four or five years of age, both boys and girls. Mean duration of treatment was about a year and a half (20.34 months, SD 18.87) and most reported diagnoses were ADHD/behavioral disorders, ASS and disorder in infancy/childhood NOS. Familial psychiatric disorders were reported in 242 families (41%). These findings are discussed in the light of earlier research

Functional Gene-Expression Analysis Shows Involvement of Schizophrenia-Relevant Pathways in Patients with 22q11 Deletion Syndrome

22q11 Deletion Syndrome (22q11DS) is associated with dysmorphology and a high prevalence of schizophrenia-like symptoms. Several genes located on chromosome 22q11 have been linked to schizophrenia. The deletion is thought to disrupt the expression of multiple genes involved in maturation and development of neurons and neuronal circuits, and neurotransmission. We investigated whole-genome gene expression of Peripheral Blood Mononuclear Cells (PBMC's) of 8 22q11DS patients and 8 age- and gender-matched controls, to (1) investigate the expression levels of 22q11 genes and (2) to investigate whether 22q11 genes participate in functional genetic networks relevant to schizophrenia. Functional relationships between genes differentially expressed in patients (as identified by Locally Adaptive Statistical procedure (LAP) or satisfying p<0.05 and fold-change >1.5) were investigated with the Ingenuity Pathways Analysis (IPA). 14 samples (7 patients, 7 controls) passed quality controls. LAP identified 29 deregulated genes. Pathway analysis showed 262 transcripts differentially expressed between patients and controls. Functional pathways most disturbed were cell death, cell morphology, cellular assembly and organization, and cell-to-cell signaling. In addition, 10 canonical pathways were identified, among which the signal pathways for Natural Killer-cells, neurotrophin/Trk, neuregulin, axonal guidance, and Huntington's disease. Our findings support the use of 22q11DS as a research model for schizophrenia. We identified decreased expression of several genes (among which COMT, Ufd1L, PCQAP, and GNB1L) previously linked to schizophrenia as well as involvement of signaling pathways relevant to schizophrenia, of which Neurotrophin/Trk and neuregulin signaling seems to be especially notable

A Network of Psychopathological, Cognitive, and Motor Symptoms in Schizophrenia Spectrum Disorders

Schizophrenia spectrum disorders (SSDs) are complex syndromes involving psychopathological, cognitive, and also motor symptoms as core features. A better understanding of how these symptoms mutually impact each other could translate into diagnostic, prognostic, and, eventually, treatment advancements. The present study aimed to: (1) estimate a network model of psychopathological, cognitive, and motor symptoms in SSD; (2) detect communities and explore the connectivity and relative importance of variables within the network; and (3) explore differences in subsample networks according to remission status. A sample of 1007 patients from a multisite cohort study was included in the analysis. We estimated a network of 43 nodes, including all the items from the Positive and Negative Syndrome Scale, a cognitive assessment battery and clinical ratings of extrapyramidal symptoms. Methodologies specific to network analysis were employed to address the study’s aims. The estimated network for the total sample was densely interconnected and organized into 7 communities. Nodes related to insight, abstraction capacity, attention, and suspiciousness were the main bridges between network communities. The estimated network for the subgroup of patients in remission showed a sparser density and a different structure compared to the network of nonremitted patients. In conclusion, the present study conveys a detailed characterization of the interrelations between a set of core clinical elements of SSD. These results provide potential novel clues for clinical assessment and intervention

Validation and recalibration of OxMIV in predicting violent behaviour in patients with schizophrenia spectrum disorders

Oxford Mental Illness and Violence (OxMIV) addresses the need in mental health services for a scalable, transparent and valid tool to predict violent behaviour in patients with severe mental illness. However, external validations are lacking. Therefore, we have used a Dutch sample of general psychiatric patients with schizophrenia spectrum disorders (N = 637) to evaluate the performance of OxMIV in predicting interpersonal violence over 3 years. The predictors and outcome were measured with standardized instruments and multiple sources of information. Patients were mostly male (n = 493, 77%) and, on average, 27 (SD = 7) years old. The outcome rate was 9% (n = 59). Discrimination, as measured by the area under the curve, was moderate at 0.67 (95% confidence interval 0.61–0.73). Calibration-in-the-large was adequate, with a ratio between predicted and observed events of 1.2 and a Brier score of 0.09. At the individual level, risks were systematically underestimated in the original model, which was remedied by recalibrating the intercept and slope of the model. Probability scores generated by the recalibrated model can be used as an adjunct to clinical decision-making in Dutch mental health services

The muscarinic M1 receptor modulates associative learning and memory in psychotic disorders.

BACKGROUND: Psychotic disorders are characterized by prominent deficits in associative learning and memory for which there are currently no effective treatments. Functional magnetic resonance imaging (fMRI) studies in psychotic disorders have identified deficits in fronto-temporal activation during associative learning and memory. The underlying pathology of these findings remains unclear. Postmortem data have suggested these deficits may be related to loss of muscarinic M1 receptor mediated signaling. This is supported by an in-vivo study showing improvements in these symptoms after treatment with the experimental M1/4 receptor agonist xanomeline. The current study tests whether reported deficits in fronto-temporal activation could be mediated by loss of M1 receptor signaling in psychotic disorders. METHODS: Twenty-six medication-free subjects diagnosed with a psychotic disorder and 29 age-, gender-, and IQ-matched healthy controls underwent two functional magnetic resonance imaging (fMRI) sessions, one under placebo and one under selective M1 antagonist biperiden, while performing the paired associated learning task. M1 binding potentials (BPND) were measured in the dorsolateral prefrontal cortex (DLPFC) and hippocampus using 123I-IDEX single photon emission computed tomography. RESULTS: In the subjects with psychotic disorders DLPFC hypoactivation was only found in the memory phase of the task. In both learning and memory phases of the task, M1 antagonism by biperiden elicited significantly greater hyperactivation of the parahippocampal gyrus and superior temporal gyrus in subjects with a psychotic disorders compared to controls. Greater hyperactivation of these areas after biperiden was associated with greater hippocampal M1 receptor binding during learning, with no association found with M1 receptor binding in the DLPFC. M1 receptor binding in the DLPFC was related to greater functional sensitivity to biperiden of the cingulate gyrus during the memory phase. CONCLUSION: The current study is the first to show differences in M1 receptor mediated functional sensitivity between subjects with a psychotic disorder and controls during a paired associate learning and memory task. Results point to subjects with psychotic disorders having a loss of M1 receptor reserve in temporal-limbic areas