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Preview: Schizophrenia Bulletin - current issue

Schizophrenia Bulletin Current Issue

Published: Sat, 02 Sep 2017 00:00:00 GMT

Last Build Date: Sat, 02 Sep 2017 07:46:52 GMT










Alternative Perspectives on Police Encounters and Psychotic Experiences [Invited Commentary on DeVylder et al, “Psychotic Experiences in the Context of Police Victimization”]


Being stopped by the police is almost never a welcome experience. When it happens on a fairly regular basis—as it does to young black men and to psychologically vulnerable individuals who inhabit the streets of many poor urban neighborhoods in the United States—a police encounter can be traumatic.1 The article by DeVylder and colleagues2 (this issue) goes further, presenting new evidence suggesting that certain kinds of police encounters can be so stressful that they induce psychotic experiences. The authors describe “police victimization” as a highly distressing form of “social defeat,” and they theorize that a susceptible person’s brain can respond by producing delusional beliefs and hallucinations. This does not necessarily mean that such individuals have a diagnosable psychotic disorder such as schizophrenia—indeed, most do not—but these (fairly common) psychotic-like experiences, even if transient, are very challenging and can complicate any confrontation with law enforcement.

Developing a Motor Systems Domain for the NIMH RDoC Program


During the last century, many studies have provided evidence that motor dysfunction is an important feature of neuropsychiatric disorders. Despite this, it is a relatively neglected area in mental illness research today. The extensive review of motor abnormalities in psychiatric illnesses by Peralta and Cuesta1 in this issue provides some clues as to why this may be the case. These include the fact that there are many different tools which are used to detect motor signs, and not all of them assess the same signs (supplementary tables S2 and S3). In addition, particular motor syndromes, such as catatonia, may be under-recognized in mental illnesses other than schizophrenia (eg, mood disorders, autism spectrum disorders).

Motor Abnormalities: From Neurodevelopmental to Neurodegenerative Through “Functional” (Neuro)Psychiatric Disorders


Motor abnormalities (MAs) of severe mental disorders have been traditionally neglected both in clinical practice and research, although they are an increasing focus of attention because of their clinical and neurobiological relevance. For historical reasons, most of the literature on MAs has been focused to a great extent on schizophrenia, and as a consequence their prevalence and featural properties in other psychiatric or neuropsychiatric disorders are poorly known. In this article, we evaluated the extent to which catatonic, extrapyramidal and neurological soft signs, and their associated clinical features, are present transdiagnostically.
We examined motor-related features in neurodevelopmental (schizophrenia, obsessive compulsive disorder, autism spectrum disorders), “functional” (nonschizophrenic nonaffective psychoses, mood disorders) and neurodegenerative (Alzheimer’s disease) disorders. Examination of the literature revealed that there have been very few comparisons of motor-related features across diagnoses and we had to rely mainly in disorder-specific studies to compare it transdiagnostically.
One or more motor domains had a substantial prevalence in all the diagnoses examined. In “functional” disorders, MAs, and particularly catatonic signs, appear to be markers of episode severity; in chronic disorders, although with different degree of strength or evidence, all motor domains are indicators of both disorder severity and poor outcome; lastly, in Alzheimer’s disease they are also indicators of disorder progression.
MAs appear to represent a true transdiagnostic domain putatively sharing neurobiological mechanisms of neurodevelopmental, functional or neurodegenerative origin.

Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders


Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.

What Can Different Motor Circuits Tell Us About Psychosis? An RDoC Perspective


Signs of motor dysfunction are evidenced across a range of psychiatric disorders including schizophrenia. Historically, these features have been neglected but emerging theoretical and methodological advancements have shed new light on the utility of considering movement abnormalities. Indeed, the National Institute of Mental Health Research Domain Criteria initiative has recently met to develop a Motor Systems Domain. This reflects a growing appreciation for the enhanced reliability and validity that can come along with evaluating disturbances relevant to psychiatric illnesses from multiple levels of analysis, and conceptualizing these domains with respect to the complexity of their role in a broader integrated system (ie, weighing contributions and interactions between the cognitive, affective, and motor domains). This article discusses motor behaviors and seeks to explain how research into basal ganglia, cerebellar, and cortico-motor circuit function/dysfunction, grounded in brain circuit-motor behavior relationships, can elucidate our understanding of pathophysiology, provide vital links to other key systems of interest, significantly improve identification and classification, and drive development of targeted individualized treatments.

Motor Issues in the Clinical High Risk Phase of Psychosis


A reliable body of research suggests that reducing the duration of untreated psychosis among those in their first episode results in demonstrable gains in clinical and functional outcomes. Along a similar line, growing evidence suggests that intervention in the Clinical High-Risk (CHR)/Ultra High-Risk phase of illness may be associated with positive outcomes including symptom improvement, delay of onset, and potential prevention of diagnosable psychosis. Early intervention in this phase of illness, however, remains controversial given that conversion rates from a typically defined risk state to diagnosable psychosis remain well below a clinically useful threshold (~36% over 3 years), and conversion itself may not be an optimal endpoint of which to predict. Nonetheless, as the risk state represents a clinically meaningful condition regardless of conversion or outcome (due to distress and impairment associated with risk symptoms), interventions that are low risk (eg, cognitive behavior therapy), low stigma, developmentally tailored, and personalized with respect to clinical targets and functional goals provide a foundation for early intervention. At present, however, treatment efforts are nonspecific, lacking precision with respect to client need (eg, psychosis vs other mental/behavioral health outcomes; see Peralta and Cuesta, this issue).1 Improved predictive accuracy for the array of possible clinical outcomes is needed to enhance prevention/intervention effectiveness.

Adherence to Antipsychotic Medication and Criminal Recidivism in a Canadian Provincial Offender Population


Preliminary evidence suggests that adherence to antipsychotic medication reduces criminal recidivism among patients diagnosed with schizophrenia. However, existing studies operationalize antipsychotic adherence as a binary variable (usually using a threshold of ≥80%), which does not reflect the prevalence of suboptimal adherence in real-world settings. The purpose of the current analysis was to investigate the association between successive ordinal levels of antipsychotic adherence and criminal recidivism in a well-defined sample of offenders diagnosed with schizophrenia (n = 11462). Adherence was measured using the medication possession ratio (MPR) and analyzed as a time-dependent covariate in multivariable regression models. Data were drawn from linked, comprehensive diagnostic, pharmacy and justice system records, and individuals were followed for an average of 10 years. Adjusted rate ratios (ARR) and confidence intervals (CI) are reported. Overall mean MPR was 0.41. Increasing levels of antipsychotic adherence were not associated with progressively lower rates of offending. However, when compared to the reference group (MPR ≥ 80%) all lower adherence levels were significantly associated (P < .001) with increased risk of violent (ARR = 1.58; 95% CI = 1.46–1.71) and nonviolent (ARR = 1.41; 95% CI = 1.33–1.50) offenses. Significance was replicated in separate sensitivity analyses. Previously published studies reporting reductions in crime may have been influenced by antipsychotic adherence ≥80%. Binary operationalization of adherence is an inaccurate predictor of recidivism. Future research addressing functional outcomes of antipsychotic adherence should conceptualize adherence as an incremental independent variable.

Aggressive Behavior Among Persons With Schizophrenia and Those Who Are Developing Schizophrenia: Attempting to Understand the Limited Evidence on Causality


People with, and those who are developing, schizophrenia are at increased risk to engage in aggressive behavior (AGB). Some incidents lead to criminal prosecution. Most people with schizophrenia who commit crimes engage in delinquency and/or AGB prior to first episode. A large proportion of these individuals have a history of childhood conduct disorder (CD) and brain abnormalities suggestive of abnormal neural development distinctive from that of others with schizophrenia. Factors contributing to schizophrenia that is preceded by CD include failing to learn not-to-behave aggressively in early childhood, impairments in understanding emotions in the faces of others, maltreatment, and subsequent re-victimization. Others with no history of antisocial behavior begin engaging in AGB as positive symptoms increase and illness onsets. They too are at elevated risk to be victimized. Specific genetic variants linked to stress regulation in combination with adversity have been associated both with AGB and psychotic symptoms. Effectively treating conduct problems and preventing victimization would reduce AGB by persons with schizophrenia.

Neighborhood Influences on Violent Reoffending Risk in Released Prisoners Diagnosed With Psychotic Disorders


Released prisoners diagnosed with psychotic disorders have elevated rates of violent reoffending risk and their exposure to adverse neighborhood environments may contribute to this risk. We identified all released sentenced prisoners in Sweden between 2003 and 2013 (n = 47226) and followed them up for a median period of 4.4 years. We identified prisoners who had ever been diagnosed with a psychotic disorder (n = 3782) or prescribed antipsychotics (n = 7366). We examined 3 neighborhood characteristics: income, proportion of welfare recipients, and crime rate. By fitting generalized mixed-effects and negative binomial regression models and adopting within-individual designs that controlled for all time-invariant unmeasured confounders within each individual, we estimated neighborhood intraclass correlations (ICCs) and associations between specific neighborhood characteristics and violent reoffending. Neighborhood factors explained 13.5% (95% CI: 10.9%; 16.6%) of the violent reoffending risk among released prisoners diagnosed with psychotic disorders. This contrasted with 4.3% (95% CI: 3.7%; 4.9%) in all released prisoners. However, after controlling for unmeasured confounding, these estimates were not statistically significant (ICCpsychotic disorders = 0.9%; 95% CI: −0.8%; 2.3%; ICCall prisoners = 0.3%; 95% CI: −0.02%; 0.6%). Similarly, none of the within-individual correlations between the specific neighborhood factors and violent reoffending were significantly different from zero. We found consistent results when we investigated prisoners with other psychiatric and substance use disorders. These findings suggest that placing released prisoners with psychotic disorders in less deprived neighborhoods might not reduce their violent reoffending risk, which may also apply to other psychiatric disorders. The assessment, treatment, and community linkage of high-risk prisoners as a strategy to reduce reoffending needs further research.

Aberrant White Matter Microstructure in Children and Adolescents With the Subtype of Prader–Willi Syndrome at High Risk for Psychosis


Prader–Willi Syndrome (PWS) is a complex neurogenetic disorder caused by loss of the paternal 15q11.2–q13 locus, due to deletion (DEL), maternal uniparental disomy (mUPD), or imprinting center defects. Individuals with mUPD have up to 60% risk of developing psychosis in early adulthood. Given the increasing evidence for white matter abnormalities in psychotic disorders, we investigated white matter microstructure in children and adolescents with PWS, with a particular emphasis on the DEL and mUPD subtypes. Magnetic resonance diffusion weighted images were acquired in 35 directions at 3T and analyzed using fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values obtained by tract-based spatial statistics (TBSS) in 28 children and adolescents with PWS and 61 controls. In addition, we employed a recently developed white matter pothole approach, which does not require local FA differences to be spatially co-localized across subjects. After accounting for age and gender, individuals with PWS had significantly lower global FA and higher MD, compared with controls. Individuals with mUPD had lower FA in multiple regions including the corpus callosum, cingulate, and superior longitudinal fasciculus and larger potholes, compared with DEL and controls. The observed differences in individuals with mUPD are similar to the white matter abnormalities in individuals with psychotic disorders. Conversely, the subtle white matter abnormalities in individuals with DEL are consistent with their substantially lower risk of psychosis. Future studies to investigate the specific neurobiological mechanism underlying the differential psychosis risk between the DEL and mUPD subtypes of PWS are highly warranted.

Psychotic Experiences in the Context of Police Victimization: Data From the Survey of Police–Public Encounters


Social defeat has been proposed as the common mechanism underlying several well-replicated risk factors for sub-threshold psychotic experiences (PEs) identified in epidemiological research. Victimization by the police may likewise be socially defeating among vulnerable individuals and, therefore, may be associated with elevated risk for PEs. However, no prior studies have examined the relation between police victimization and PEs. We tested the hypothesis that exposure to police victimization (ie, physical, sexual, psychological, and neglect) would be associated with increased odds for PEs in the Survey of Police–Public Encounters data (N = 1615), a general population sample of adults from 4 US cities. Respondents who reported each type of police victimization were more likely to report PEs in logistic regression analyses (all P < .01), most of which were significant even when adjusting for demographic variables, psychological distress, and self-reported crime involvement (adjusted OR range: 1.30 to 7.16). Furthermore, the prevalence of PEs increased with greater exposure to police victimization in a linear dose-response relation, OR (95% CI) = 1.44 (1.24–1.66). These findings suggest that police victimization is a clinically important and previously unreported risk factor for PEs in the urban US population. These findings support the need for community-based outreach efforts and greater police training to reduce the prevalence of this exposure, particularly in socially disadvantaged urban communities.

Effects of Augmenting N -Methyl-D-Aspartate Receptor Signaling on Working Memory and Experience-Dependent Plasticity in Schizophrenia: An Exploratory Study Using Acute d -cycloserine


Cognitive deficits in schizophrenia have been hypothesized to reflect N-methyl-D-aspartate receptor (NMDAR) dysfunction. However, the mechanisms through which the NMDAR contributes to individual cognitive functions differ. To explore how NMDAR signaling relates to specific cognitive deficits in schizophrenia, we tested the effects of enhancing NMDAR signaling on working memory and experience-dependent plasticity using d-cycloserine (DCS). Plasticity was assessed using an EEG paradigm that utilizes high-frequency visual stimulation (HFvS) to induce neural potentiation, and 2 learning tasks, the information integration (IIT) and weather prediction (WPT) tasks. Working memory was assessed using an N-back task. Forty-five schizophrenia patients were randomized to receive a single 100 mg DCS dose (SZ-DCS; n = 24) or placebo (SZ-PLC; n = 21) in a double-blind, between-groups design. Testing occurred on a single day after placebo or DCS administration; baseline values were not obtained. DCS did not affect plasticity, as indicated by similar neural potentiation, and similar IIT and WPT learning between groups. However, among patients who successfully engaged in the working memory task (ie, performed above chance), SZ-DCS (n = 17) showed superior 2-back performance compared to SZ-PLC (n = 16). Interestingly, SZ-DCS also showed larger pre-HFvS neural responses during the LTP task. Notably, this pattern of DCS effects is the opposite of those found in our prior study of healthy adults. Results are consistent with target engagement of the NMDAR by DCS, but suggest that NMDAR signaling was not translated into synaptic plasticity changes in schizophrenia. Results highlight the importance of considering how distinct NMDAR-associated processes contribute to individual cognitive deficits in schizophrenia.

Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1


Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain. Across 2 different sites and protocols, Nrg1 mutants demonstrated deficits in prepulse inhibition, a measure of sensorimotor gating, that is, disrupted in schizophrenia; these deficits were partially reversed by acute treatment with second, but not first-, generation antipsychotic drugs. However, Nrg1 mutants did not show a specific deficit in latent inhibition, a measure of selective attention that is also disrupted in schizophrenia. In contrast, in a “what–where–when” object recognition memory task, Nrg1 mutants displayed sex-specific (males only) disruption of “what–when” performance, indicative of impaired temporal aspects of episodic memory. Differential metabolomic profiling revealed that these behavioral phenotypes were accompanied, most prominently, by alterations in lipid metabolism pathways. This study is the first to associate these novel physiological mechanisms, previously independently identified as being abnormal in schizophrenia, with disruption of NRG1 function. These data suggest novel mechanisms by which compromised neuregulin function from birth might lead to schizophrenia-relevant behavioral changes in adulthood.

IQ, the Urban Environment, and Their Impact on Future Schizophrenia Risk in Men


Exposure to an urban environment during early life and low IQ are 2 well-established risk factors for schizophrenia. It is not known, however, how these factors might relate to one another. Data were pooled from the North Jutland regional draft board IQ assessments and the Danish Conscription Registry for men born between 1955 and 1993. Excluding those who were followed up for less than 1 year after the assessment yielded a final cohort of 153170 men of whom 578 later developed a schizophrenia spectrum disorder. We found significant effects of having an urban birth, and also experiencing an increase in urbanicity before the age of 10 years, on adult schizophrenia risk. The effect of urban birth was independent of IQ. However, there was a significant interaction between childhood changes in urbanization in the first 10 years and IQ level on the future adult schizophrenia risk. In short, those subjects who moved to more or less urban areas before their 10th birthday lost the protective effect of IQ. When thinking about adult schizophrenia risk, the critical time window of childhood sensitivity to changes in urbanization seems to be linked to IQ. Given the prediction that by 2050, over 80% of the developed world’s population will live in an urban environment, this represents a major future public health issue.

Altered DLPFC–Hippocampus Connectivity During Working Memory: Independent Replication and Disorder Specificity of a Putative Genetic Risk Phenotype for Schizophrenia


Altered connectivity of dorsolateral prefrontal cortex (DLPFC) and hippocampus during working memory is considered an intermediate phenotype for schizophrenia (SCZ), but the relevance for other mental disorders with shared genetic background remains unknown. Here we investigated its presence in unaffected first-degree relatives of patients with bipolar disorder (BD) or major depressive disorder (MDD). Furthermore, we aimed to provide an independent replication of this phenotype in first-degree relatives of SCZ patients. We acquired functional magnetic resonance imaging (fMRI) data from 309 healthy controls and 218 healthy first-degree relatives of index patients with SCZ (n = 62), BD (n = 66) and MDD (n = 90), who completed the n-back working memory paradigm. We observed a significant group effect on DLPFC–hippocampus coupling (PFWE = .031, all P-values region of interest [ROI] corrected). Post hoc comparisons revealed that this effect was driven by the SCZ relatives, who showed a significant increase in the negative functional connectivity of the DLPFC and right hippocampus compared to controls (PFWE = .001), BD relatives (PFWE = .015) and trend-wise also MDD relatives (PFWE = .082). Comparison of BD and MDD relatives to the controls revealed no difference (PFWE-values > .451). Supplementary analyses suggested that the SCZ relatives finding is robust to a range of potential confounds, including structural differences. Our data further support altered DLPFC–hippocampus connectivity during working memory as an intermediate phenotype for SCZ. This suggests that this phenotype is relatively specific to SCZ and does not translate to other genetically related disorders in the mood-psychosis spectrum.

Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study


Nearly one-third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop a psychotic disorder during life, most of them by early adulthood. Importantly, a full-blown psychotic episode is usually preceded by subthreshold symptoms. In the current study, 760 participants (aged 6–55 years) with a confirmed hemizygous 22q11.2 microdeletion have been recruited through 10 medical sites worldwide, as part of an international research consortium. Of them, 692 were nonpsychotic and with complete measurement data. Subthreshold psychotic symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). Nearly one-third of participants met criteria for positive subthreshold psychotic symptoms (32.8%), less than 1% qualified for acute positive subthreshold symptoms, and almost a quarter met criteria for negative/disorganized subthreshold symptoms (21.7%). Adolescents and young adults (13–25 years) showed the highest rates of subthreshold psychotic symptoms. Additionally, higher rates of anxiety disorders and attention deficit/hyperactivity disorder (ADHD) were found among the study participants with subthreshold psychotic symptoms compared to those without. Full-scale IQ, verbal IQ, and global functioning (GAF) scores were negatively associated with participants’ subthreshold psychotic symptoms. This study represents the most comprehensive analysis reported to date on subthreshold psychosis in 22q11.2DS. Novel findings include age-related changes in subthreshold psychotic symptoms and evidence that cognitive deficits are associated with subthreshold psychosis in this population. Future studies should longitudinally follow these symptoms to detect whether and how early identification and treatment of these manifestations can improve long-term outcomes in those that eventually develop a psychotic disorder.

Polygenic Risk Score for Schizophrenia and Treatment-Resistant Schizophrenia


Treatment-resistant schizophrenia (TRS) affects around one-third of individuals with schizophrenia. Although a number of sociodemographic and clinical predictors of TRS have been identified, data on the genetic risk of TRS are sparse. We aimed to investigate the association between a polygenic risk score for schizophrenia and treatment resistance in patients with schizophrenia. We conducted a nationwide, population-based follow-up study among all Danish individuals born after 1981 and with an incident diagnosis of schizophrenia between 1999 and 2007. Based on genome-wide data polygenic risk scores for schizophrenia were calculated in 862 individuals with schizophrenia. TRS was defined as either clozapine initiation or at least 2 periods of different antipsychotic monotherapies and still being hospitalized. We estimated hazard rate ratios (HRs) for TRS in relation to the polygenic risk score while adjusting for population stratification, age, sex, geographical area at birth, clinical treatment setting, psychiatric comorbidity, and calendar year. Among the 862 individuals with schizophrenia, 181 (21.0%) met criteria for TRS during 4674 person-years of follow-up. We found no significant association between the polygenic risk score and TRS, adjusted HR = 1.13 (95% CI: 0.95–1.35). Based on these results, the use of the polygenic risk score for schizophrenia to identify individuals with TRS is at present inadequate to be of clinical utility at the individual patient level. Future research should include larger genetic samples in combination with non-genetic markers. Moreover, a TRS-specific developed polygenic risk score would be of great interest towards early prediction of TRS.

Striatal and Extrastriatal Dopamine Transporter Availability in Schizophrenia and Its Clinical Correlates: A Voxel-Based and High-Resolution PET Study


Neuroimaging studies investigating dopamine (DA) function widely support the hypothesis of presynaptic striatal DA hyperactivity in schizophrenia. However, published data on the striatal DA transporter (DAT) appear less consistent with this hypothesis, probably partly due to methodological limitations. Moreover, DAT in extrastriatal regions has been very poorly investigated in the context of schizophrenia. In order to address these issues, we used a high resolution positron emission tomograph and the selective DAT radioligand [11C]PE2I, coupled with a whole brain voxel-based analysis method to investigate DAT availability in striatal but also extra-striatal regions in 21 male chronic schizophrenia patients compared to 30 healthy male controls matched by age. We found higher DAT availability in schizophrenia patients in midbrain, striatal, and limbic regions. DAT availability in amygdala/hippocampus and putamen/pallidum was positively correlated with hallucinations and suspiciousness/persecution, respectively. These results are consistent with an increase of presynaptic DA function in patients with schizophrenia, and support the involvement of both striatal and extrastriatal DA dysfunction in positive psychotic symptoms. The study also highlights the whole brain voxel-based analysis method to explore DA dysfunction in schizophrenia.

Childhood Maltreatment and Young Adulthood Hallucinations, Delusional Experiences, and Psychosis: A Longitudinal Study


Child maltreatment is a widespread public health problem associated with a range of mental health disorders later in life. In order to effectively address these disorders, there is a need to understand more about the mental health consequences of different types of child maltreatment. This study examines the associations between prospectively substantiated child maltreatment (ages 0–14 y) and reports of hallucinations and delusional experiences at 21 years after birth. As well, we examined 12-month and lifetime psychotic disorders using data from a longitudinal birth cohort. The study comprised 3752 participants from the Mater-University of Queensland Study of Pregnancy, a prospective Australian prebirth cohort study. Psychotic experiences and 12-month and lifetime psychosis were measured using the Achenbach Young Adults Self-Report, the Peter’s Delusions Inventory, and Composite International Diagnostic Interview at the 21-year follow-up. In adjusted analyses, those children who had experienced any maltreatment and who were emotionally abused and neglected were more likely to report (1) hallucinations and lifetime delusional experiences and (2) more likely to experience lifetime psychosis than their nonabused counterparts. In expanded models, those exposed to multiple forms of maltreatment, in particular with emotional abuse and neglect, had an increased likelihood of hallucinations and delusional experiences. There is an association between child maltreatment, especially emotional abuse and neglect, and later hallucinations, delusional experiences, and psychosis. It is, however, relevant to note that the vast majority of children experiencing childhood maltreatment do not appear to develop psychotic experiences or psychotic disorder. Further research to determine the reasons for highly variable outcomes of child maltreatment is warranted.

Mild Depressive Symptoms Mediate the Impact of Childhood Trauma on Long-Term Functional Outcome in Early Psychosis Patients


The mechanism linking childhood trauma (CT) to the functional deficits observed in early psychosis (EP) patients is as yet unknown. We aim to examine the potential mediating effect of depressive symptoms in this well-established association.
Two hundred nine EP subjects aged 18–35 were assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Patients were classified into early trauma if they had faced at least one experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) before age 12, and late trauma if the exposure had occurred between ages 12 and 16. Diagnosis was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Psychopathology was assessed with the Positive and Negative Syndrome Scale and the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order to study whether the relationship between CT and functioning was mediated by depressive symptoms.
When compared with nonexposed patients, early but not late trauma patients showed lower levels of GAF and SOFAS scores over all the time points, excepting after the first assessment. After 30 and 36 months, the effect of early trauma on functioning was completely mediated by depressive symptoms. No mediating effect of positive or negative symptoms was highlighted at those time points.
Mild depressive symptoms mediated the impact of early trauma on long-term functional outcome. Intensifying pharmacologic and/or psychotherapeutic treatment, focused on the depressive dimension, may help traumatized EP patients to improve their functioning.

Familial Aggregation and Heritability of Schizophrenia and Co-aggregation of Psychiatric Illnesses in Affected Families


Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia made by psychiatrists were ascertained between January 1, 1996 and December 31, 2013. Having an affected co-twin, first-degree relative, second-degree relative, or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55–46.92), 6.30 (6.09–6.53), 2.44 (1.91–3.12), and 1.88 (1.64–2.15), respectively. Compared with the general population, individuals with one affected first-degree relative had a RR (95% CI) of 6.00 (5.79–6.22) and those with 2 or more had a RR (95% CI) of 14.66 (13.00–16.53) for schizophrenia. The accountability for the phenotypic variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared environmental factors, and 37.2% for non-shared environmental factors. The RR (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49 (3.34–3.64) for mood disorders and 3.91 (3.35–4.57) for delusional disorders. A family history of schizophrenia is therefore associated with a higher risk of developing schizophrenia, mood disorders, and delusional disorders. Heritability and environmental factors each account for half of the phenotypic variance of schizophrenia.

Bullying Mediates Between Attention-Deficit/Hyperactivity Disorder in Childhood and Psychotic Experiences in Early Adolescence


Although a childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) is known to be linked to psychotic experiences and psychotic disorders in later life, the developmental trajectories that could explain this association are unknown. Using a sample from the prospective population-based Avon Longitudinal Study of Parents and Children (ALSPAC) (N = 8247), we hypothesized that the previously reported association of ADHD combined subtype in childhood and psychotic experiences in early adolescence is mediated by traumatic events and by involvement in bullying. Moreover, we expected this mediation to be specific to ADHD and tested this by comparison with specific phobia. Children with ADHD combined subtype at age 7 were more often involved in bullying at age 10 (OR 3.635, 95% CI 1.973–6.697) and had more psychotic experiences at age 12 (OR 3.362, 95% CI 1.781–6.348). Moreover, children who were involved in bullying had more psychotic experiences (2.005, 95% CI 1.684–2.388). Bullying was a significant mediator between ADHD and psychotic experiences accounting for 41%–50% of the effect. Traumatic events from birth to age 11 were also significantly associated with ADHD combined subtype and psychotic experiences; however, there was no evidence of mediation. Specific phobia was significantly associated with psychotic experiences, but not with bullying. To conclude, bullying is a relevant translating mechanism from ADHD in childhood to psychotic experiences in early adolescence. Interventions that eliminate bullying in children with ADHD could potentially reduce the risk of having psychotic experiences in later life by up to 50%. Clinicians should thus screen for bullying in routine assessments of children with ADHD.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia


Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology.

A Father’s Illness



Experiences of a First-Episode Psychosis by a Psychology Graduate Student


I grew up in a nice family home in an affluent suburb of Glasgow, achieved good grades at school, and in 2008 graduated with a good degree in Psychology, when I was accepted onto a PhD program. Yet in March 2014 I found myself in a local psychiatric hospital experiencing a psychotic episode. So what happened?

My Triumph Over Psychosis: A Journey From Schizophrenia and Homelessness to College Graduate


At age 17, I won a Presidential Scholarship to study biochemistry at my first choice, a distinguished private university in Los Angeles. As an undergraduate, I conducted research, published 3 articles in peer-reviewed journals, and served as first violinist of the community orchestra. Everyone, including myself, thought I would succeed in life. Never in my wildest dreams did I imagine I would develop delusions, start having command hallucinations, lose my scholarship, and become homeless for 4 years, without even telling my parents.