Morten Ekstrøm

Childhood Motor Coordination and Adult Schizophrenia Spectrum Disorders

OBJECTIVE The authors examined whether motor coordination difficulties assessed in childhood predict later adult schizophrenia spectrum outcomes. METHOD A standardized childhood neurological examination was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Adult diagnostic information was available for 244 members of the sample. Participants fell into three groups: children whose mothers or fathers had a psychiatric hospital diagnosis of schizophrenia (N=94); children who had at least one parent with a psychiatric record of hospitalization for a nonpsychotic disorder (N=84); and children with no parental records of psychiatric hospitalization (N=66). Psychiatric outcomes of the offspring were assessed through psychiatric interviews in 1992 when participants were 31-33 years of age, as well as through a scan of national psychiatric registers completed in May 2007. RESULTS Children who later developed a schizophrenia spectrum disorder (N=32) displayed significantly higher scores on a scale of coordination deficits compared with those who did not develop a mental illness in this category (N=133). CONCLUSIONS Results from this study provide further support for the neurodevelopmental hypothesis of schizophrenia and underscore the potential role of cerebellar and/or basal ganglia abnormalities in the etiology and pathophysiology of schizophrenia.

Perspective-taking deficits in people with schizophrenia spectrum disorders : a prospective investigation

BACKGROUND This study examined data from a Danish prospective longitudinal project in attempt to address the state/trait controversy regarding theory of mind deficits in schizophrenia. Deficits in perspective-taking--a component of theory of mind--were investigated prospectively among children who developed schizophrenia spectrum disorders as adults in comparison to children who did not develop schizophrenia spectrum disorders. METHOD A total of 265 high risk and control subjects were studied in 1972. At the time of initial assessment, the Role-Taking Task (RTT) was administered. Two hundred and forty-two of these children were evaluated in 1992 during follow-up examinations. Sixteen developed schizophrenia, 10 developed a schizophrenia spectrum disorder, 70 had outcomes of other psychopathology, and 146 did not develop a mental illness. RESULTS Children who later developed schizophrenia or a schizophrenia spectrum disorder had lower RTT scores, controlling for verbal IQ and age, compared to those who did not develop any mental illness. Although in the expected direction, RTT scores for those with schizophrenia spectrum disorders were not significantly different from those who developed a non-psychotic disorder. CONCLUSIONS Deficits in perspective-taking among children who later developed schizophrenia spectrum disorders suggest that a facet of theory of mind is impaired prior to development of schizophrenia. Our findings lend support to the hypothesis that theory of mind deficits in schizophrenia are trait markers of the disorder.

Childhood laterality and adult schizophrenia spectrum disorders: a prospective investigation

Left or mixed-handedness, footedness, and eye dominance are thought to indicate abnormalities in lateralization related to schizophrenia. Increased left or mixed-dominance in schizophrenia suggests possible hemispheric abnormalities associated with the disorder. A related body of research suggests that some indications of lateralization abnormalities may be evident prior to the onset of schizophrenia, suggesting that disruptions in lateralization are inherent to the developmental course of the disorder. We attempted to replicate and extend upon findings indicating differences in lateralization between children who later developed a schizophrenia spectrum disorder (n = 26) and those who did not develop a schizophrenia spectrum disorder (n = 216), among a high-risk and control, longitudinal sample. The rate of left or mixed-footedness, eye dominance, and any anomalous lateralization, but not handedness, discriminated between those who developed schizophrenia spectrum disorders and those who did not. Left or mixed-laterality appears to signal neurological disruption relevant to the development of schizophrenia spectrum disorders.

Premorbid IQ and adult schizophrenia spectrum disorder: verbal Performance subtests.

The present prospective high-risk study examined associations between childhood scores on five Wechsler Intelligence Scale for Children (WISC) subtests (vocabulary, similarities, block design, object assembly, and mazes) and later development of schizophrenia spectrum disorders (SSD). The sample comprised 244 high-risk or control children who were administered the WISC subtests at age 10 to 13 years in 1972. Adult psychiatric data were gathered from psychiatric interviews in 1992-93 and from the Danish Psychiatric Central Register in 2007. Thirty-two participants had developed SSD, 79 other psychiatric disorders (OPD), and 133 had no diagnosis (ND). The SSD group obtained lower scores than the ND group on all subtests and IQs, but when adjusted for sex and parental social status only significantly lower scores on similarities, object assembly, mazes, and total IQ. Compared with the ND group, the OPD group obtained significantly lower scores on similarities, vocabulary, verbal IQ, and total IQ. The only significant difference between the SSD and OPD groups was on object assembly (OPD performed at the level of ND). The results suggest a premorbid deficit in general intelligence in individuals who later develop SSD. The results for the OPD group support recent studies demonstrating that premorbid IQ deficits may characterize a wide range of psychiatric disorders.

Premorbid multivariate markers of neurodevelopmental instability in the prediction of adult schizophrenia-spectrum disorder: a high-risk prospective investigation.

The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample. Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n=94); children with a parent with a non-psychotic mental health diagnosis (n=84); and children with a parent with no records of psychiatric hospitalization (n=66). Variables measured included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a schizophrenia-spectrum disorder. Genetic risk, MPAs, and other markers of neurodevelopmental instability may be useful for comprehensive prediction models.

Premorbid teacher-rated social functioning predicts adult schizophrenia-spectrum disorder: A high-risk prospective investigation

Social functioning deficits are a core component of schizophrenia spectrum disorders, and may emerge years prior to the onset of diagnosable illness. The current study prospectively examines the relation between teacher-rated childhood social dysfunction and later mental illness among participants who were at genetic high-risk for schizophrenia and controls (n=244). The teacher-rated social functioning scale significantly predicted psychiatric outcomes (schizophrenia-spectrum vs. other psychiatric disorder vs. no mental illness). Poor premorbid social functioning appears to constitute a marker of illness vulnerability and may also function as a chronic stressor potentially exacerbating risk for illness.

Childhood dyspraxia predicts adult-onset nonaffective–psychosis-spectrum disorder

Several neurological variables have been investigated as premorbid biomarkers of vulnerability for schizophrenia and other related disorders. The current study examined whether childhood dyspraxia predicted later adult nonaffective-psychosis-spectrum disorders. From a standardized neurological examination performed with children (aged 10-13) at genetic high risk of schizophrenia and controls, several measures of dyspraxia were used to create a scale composed of face/head dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to other psychiatric disorders and no mental illness outcomes, even after controlling for genetic risk, χ2 (4, 244) = 18.61, p < .001. Findings that symptoms of dyspraxia in childhood (reflecting abnormalities spanning functionally distinct brain networks) specifically predict adult nonaffective-psychosis-spectrum disorders are consistent with a theory of abnormal connectivity, and they highlight a marked early-stage vulnerability in the pathophysiology of nonaffective-psychosis-spectrum disorders.

Premorbid personality in schizophrenia spectrum: A prospective study

Schizophrenia has been linked with premorbid character anomalies since it was first described. However, few prospective studies of premorbid personality characteristics in schizophrenia and related disorders have been conducted. This study evaluates premorbid personality in children who developed schizophrenia spectrum disorder in adult life. In 1972, 265 children at an average age of 12 (90 with at least one schizophrenic parent) from the Copenhagen Perinatal Cohort participated in a 1-day follow-up during which they were in contact with seven examiners who rated their personality by means of an Adjective Check List (ACL). In 1991–93, adult psychiatric status was assessed for 242 of these individuals, who were classified into three categories: schizophrenia spectrum (n=24), other psychiatric diagnoses (n=72) and healthy controls (n=145). Personality characteristics derived from the ACL were linked to these three diagnostic categories. Twelve-year-old children destined to develop a disorder in the schizophrenia spectrum deviated significantly from healthy controls on a number of personality characteristics: they were rated significantly lower than controls on intelligence, concentration, maturity, friendliness, cooperation, self-control and significantly higher on aggression. Non-significant trends indicated that this group displayed more deviant personality scores than psychiatric controls. Children who later develop schizophrenia spectrum disorder differed from normal controls with respect to a number of personality traits. The ACL may be too insensitive to discriminate between premorbid personality in the schizophrenia spectrum and other psychopathology.

Childhood pegboard task predicts adult-onset psychosis-spectrum disorder among a genetic high-risk sample

Motor abnormalities have been established as a core aspect of psychosis-spectrum disorders, with numerous studies identifying deficits prior to clinical symptom presentation. Additional research is needed to pinpoint standardized motor assessments associated with psychosis-spectrum disorders prior to illness onset to enhance prediction and understanding of etiology. With a long history of findings among people with diagnosable psychosis-spectrum disorders, but little research conducted during the premorbid phase, pegboard tasks are a viable and understudied measure of premorbid for psychosis motor functioning. In the current study, examining data from the Copenhagen Perinatal Cohort, the Simultaneous Pegs Test was performed with children (n=244, aged 10-13) at genetic high risk for psychosis (n=94) and controls (n=150). Findings suggest that children who eventually developed a psychosis-spectrum disorder (n=33) were less likely to successfully complete the task within time limit relative to controls (χ2(2, N=244)=6.94, p=0.03, ϕ=0.17). Additionally, children who eventually developed a psychosis-spectrum disorder took significantly longer to complete the task relative to controls (χ2(2, N=244)=7.06, p=0.03, ϕ=0.17). As pegboard performance is thought to tap both diffuse and specific brain networks, findings suggest that pegboard tests may be useful premorbid measures of motor functioning among those on a trajectory towards a psychosis-spectrum disorder.

Treatment of traumatized refugees with Sertraline versus Venlafaxine in combination with psychotherapy - study protocol for a randomized clinical trial: Study protocol for a randomized clinical trial

BackgroundSufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially Sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder.DesignThis study will include approximately 150 patients, randomized into two different groups treated with either Sertraline or Venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors.DiscussionThis study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines.Trial registrationClinicalTrials.gov NCT01569685