Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives

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.     

Psychopathology among offspring of parents with schizophrenia: relationship to premorbid impairments

INTRODUCTION: A broad range of psychopathology, including externalizing disorders is seen in offspring at genetic risk for schizophrenia. However, it is unclear whether such psychopathology may underlie a higher predisposition to the premorbid antecedents of schizophrenia. We examined the prevalence and correlates of psychopathology in an ongoing study of offspring genetically at risk for schizophrenia. METHODS: Seventy five consenting high risk offspring (HR: offspring, age 15.68+/-3.27 years; male/female 34/41) and 82 matched comparison subjects (40 males and 42 females; age 15.92+/-3.0 years) participated in this study. Diagnoses were ascertained using structured psychiatric interviews and consensus meetings, including all available clinical information. RESULTS: Sixty (60%) of the HR offspring had one or more lifetime diagnosis of axis I psychiatric disorder. HR subjects with axis I psychopathology had significantly more soft neurological signs, poorer premorbid adjustment, and higher schizotypy scores as measured by Chapman psychosis proneness scales. Among those with psychopathology, HR subjects with externalizing disorders showed the most abnormal scores in schizotypy. DISCUSSION: A substantial proportion of HR offspring of parents with schizophrenia manifest a broad range of childhood psychiatric disorders. Psychopathology, especially externalizing disorders such as attention deficit hyperactivity disorder (ADHD) may represent a subgroup with an increased risk for schizophrenia spectrum disorders. This possibility needs to be examined by prospective follow-up studies, and would be of considerable importance to early diagnosis and intervention efforts in schizophrenia.     

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.     

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.     

Neurobehavioral deficits in young adult offspring with heightened risk for psychosis who developed schizophrenia-spectrum disorder

Neurobehavioral deficits in neuromotor function, verbal memory, executive function and attention found in patients with schizophrenia and their relatives have been suggested to be liability indicators or predictors of schizophrenia. It remains uncertain which of these neurobehavioral deficits are components of the illness itself or characteristics associated with genetic risk for it. The purpose of this study was to investigate the relation between these neurobehavioral deficits and schizophrenia-spectrum disorder in young adults at genetic risk for psychosis. A 93%-effective follow-up (total n=166, mean 22.4 yr of age) of a sample longitudinally investigated since fetal age provided complete data for mental disturbance, neuropsychological performance and neurological abnormality for 74 offspring at increased risk for psychosis (38 offspring of mothers with schizophrenia and 36 offspring of mothers with affective psychosis) and 88 normal-risk offspring. Abnormal glabella reflex and deficits in verbal memory, attention and complex executive functions seem specifically to be related to schizophrenia-spectrum disorder (primarily Cluster A personality disorders) among offspring at genetic risk for psychosis, while neurobehavioral deficits in general characterized offspring at heightened (vs. normal) genetic risk for psychosis, with no relation to schizophrenia-spectrum disorders. The two patterns of neurobehavioral deficits observed here may possibly reflect different causes and different aspects of a deviant neurodevelopmental process, and potentially contribute to a more nuanced version of this all-pervasive (but often non-specific) "model" of schizophrenia's development.     

Childhood videotaped social and neuromotor precursors of schizophrenia: a prospective investigation

OBJECTIVE: The authors examined videotaped behaviors of children who developed schizophrenia as adults and of comparison subjects to disclose possible social and neuromotor deficits foreshadowing later development of schizophrenia. METHOD: In 1972, a sample of 265 11-13-year-old Danish children were filmed under standardized conditions while they were eating lunch. The examination was part of a larger study investigating early signs of schizophrenia spectrum disorders. Many of the subjects had a parent with schizophrenia, leaving them at high risk for developing a schizophrenia spectrum disorder. In 1991, adult psychiatric outcome data were obtained for 91.3% (N=242). This study systematically analyzed the videotapes to determine whether the children who developed schizophrenia as adults evidenced greater social and/or neuromotor deficits than children who did not develop a psychiatric disorder and children who developed other psychiatric disorders. RESULTS: The findings from this study suggest that the brief videotaped footage of children eating lunch was able to discriminate between the individuals who later developed schizophrenia and those who did not. Specifically, the preschizophrenia children evidenced differences on measures of sociability and general neuromotor functioning (among boys) from the children who developed other psychiatric disorders and the children who did not develop a psychiatric disorder. CONCLUSIONS: Social and neuromotor deficits specific to children who develop schizophrenia in adulthood provide further support for a neurodevelopmental hypothesis of schizophrenia.     

Effects of child-rearing by schizophrenic mothers: a 25-year follow-up

We conducted a 25-year follow-up study of 50 children of schizophrenic mothers, consisting of 25 children reared by their mothers and 25 children reared apart. The children's adult psychiatric status was evaluated in a 3-h structured interview employing a battery of syndrome check-lists and scales. A slightly higher incidence of psychopathology (including schizophrenia-spectrum disorders) was found among the reared-apart subjects. This may possibly be attributed to their greater genetic predisposition, as suggested by their mothers' more severe illnesses. Lifetime diagnoses do not provide evidence that psychopathology in offspring at genetic risk is increased by rearing by a schizophrenic mother.     

Premorbid performance IQ deficit in schizophrenia

OBJECTIVE: Performance IQ (PIQ) is often lower than verbal IQ (VIQ) in schizophrenic patients. Whether PIQ < VIQ precedes psychotic symptoms in schizophrenia remains uncertain. METHOD: We investigated premorbid IQ scores in 63 subjects assessed at a child and adolescent psychiatric unit (mean age 13.1 years, SD 3.2), who at follow-up in adulthood (mean age 30.9 years, SD 3.9) received a lifetime RDC diagnosis of schizophrenia-related psychosis, affective disorder, or no psychiatric disorder. RESULTS: Premorbid PIQ < VIQ significantly differentiated the groups with schizophrenia-related psychosis and no psychiatric disorder. Subjects with schizophrenia-related psychosis had a significantly lower mean value for premorbid PIQ, but not VIQ, compared to subjects who developed affective disorder or subjects without psychiatric disorder. CONCLUSION: Our results emphasize premorbid intellectual deficits in schizophrenia. Those deficits might largely be in consequence of an impairment on the PIQ scale.     

Clinical Correlates of Childhood Trauma and Dissociative Phenomena in Patients with Severe Psychiatric Disorders

In this present study, we aim to investigate the possibility of a link between psychotic disorders and traumatic experiences in a group of female patients diagnosed with psychotic disorders by comparing childhood trauma exposure with a group of non-psychotic psychiatric disorder attending the same pschiatric clinic. Secondary purpose of this study is to examine the clinical correlates of trauma exposure, dissociative phenomena and psychiatric symptomatology between these two group of patients. Two psychiatric sample groups, those with psychotic disorders—mostly schizophrenic—(n = 54), and those with a non-psychotic severe psychiatric disorders (n = 24), were recruited. Data were collected for demographic, psychiatric and trauma histories and psychiatric symptomatology for all patients. In this study, high prevalance rates of childhood traumatic experiences and dissociative phenomena were found in both groups. Total scores of childhood trauma questionnaire in favor of the non-psychotic group were found to be close to significance (p = 0.052). DES scores of non-psychotic group were also higher although not statistically significant. 54.2 % of nonpsychotic cases had DES scores >20 on the other hand, that percentage of psychotic cases were found to be as 38.9 %. Furthermore, psychiatric patients who have suffered childhood traumatic experiences are far more likely to try to kill themselves than psychiatric patients who have not experienced such abuse. The high rates of childhood traumatic events in our present samples of both schizophrenia-spectrum patients and nonpsychotic patients confirm the need for clinicans to take trauma histories routinely.     

Temperament and character as schizophrenia-related endophenotypes in non-psychotic siblings

BACKGROUND: Quantitative endophenotypes are needed to better understand the pathogenesis of schizophrenia. The psychobiological model of temperament and character suggests that personality traits are heritable and regulated by brain systems influencing schizophrenia susceptibility. Thus, measures of temperament and character may serve as schizophrenia-related endophenotypes in individuals with schizophrenia and their non-psychotic siblings. METHODS: Individuals with schizophrenia (n=35), their non-psychotic siblings (n=34), controls (n=63), and their siblings (n=56) participated in a study of the clinical, neurocognitive and neuromorphological characteristics of schizophrenia. A mixed-model approach assessed group differences on the Temperament and Character Inventory (TCI). Neurocognitive deficits and psychopathology were correlated with the TCI. Configurations of TCI domains were examined using a generalized linear model. RESULTS: Individuals with schizophrenia and their non-psychotic siblings had higher harm avoidance than controls and their siblings. Individuals with schizophrenia had lower self-directedness and cooperativeness, and higher self-transcendence than their non-psychotic siblings, controls, and the siblings of controls. Neurocognition was not related to temperament and character in individuals with schizophrenia or either control group. In non-psychotic siblings, self-directedness and cooperativeness were correlated with working memory and crystallized IQ. CONCLUSION: Evidence supports harm avoidance as a schizophrenia-related endophenotype. An increased risk of schizophrenia may be associated with asociality (configured as high harm avoidance and low reward dependence), schizotypy (configured as low self-directedness, low cooperativeness, and high self-transcendence), and neurocognitive deficits (poor executive functioning, working/episodic memory, attention, and low IQ). The non-psychotic siblings demonstrated features of a mature character profile including strong crystallized IQ, which may confer protection against psychopathology.     

A prospective study of offspring of women with psychosis: visual dysfunction in early childhood predicts schizophrenia-spectrum disorders in adulthood

OBJECTIVE: Children with visual dysfunction have perinatal, neurological, visual-perceptual and cognitive abnormalities, similar to schizophrenia patients. We prospectively investigated whether visual dysfunction in childhood selectively predicts adult schizophrenia-spectrum disorders, and is related to childhood neurological abnormality. METHOD: Offspring of mothers with and without a history of psychosis were prospectively assessed with vision tests at 4 years, neurological examinations at 6 years, and interviews for psychiatric disorders at follow-up (93% effective, n=166) at 22 years. RESULTS: In the total sample and high-risk (HR) offspring, visual dysfunction at 4 years, and its severity, were associated only with schizophrenia-spectrum disorders in adulthood, and with neurological abnormality at 6 years. CONCLUSION: Visual dysfunction at 4 years of age selectively predicts schizophrenia-spectrum disorders in adulthood among HR offspring, this likely reflecting disturbed neurological development.     

The course and clinical correlates of dysfunctions in visual perceptual organization in schizophrenia during the remission of psychotic symptoms

This study evaluated deficits in visual perceptual organization in schizophrenia over the course of inpatient treatment, in relation to the remission of particular psychotic symptoms. Disorganized (n=14) and non-disorganized (n=33) schizophrenia patients were tested upon admission to an inpatient psychiatric unit, and again after 3 weeks of treatment, on two measures of visual perceptual organization. Performance of schizophrenia patients was compared to groups of patients with psychotic disorders other than schizophrenia (n=19) and non-psychotic psychiatric disorders (n=25). Symptom ratings were collected at both assessment points. Deficits in visual perceptual organization were observed for both tasks in disorganized schizophrenia patients at index and these deficits improved during the course of treatment. Moreover, improvement in visual perceptual organization correlated significantly with reductions in disorganized symptoms in the schizophrenia group. We interpret these data as further support for the hypothesis that the disorganization syndrome in schizophrenia reflects a widespread deficit in the cognitive coordination of contextually related stimuli, leading to dysfunctional organization of stimulus features in vision, thought and language.     

Diagnostic specificity of poor premorbid adjustment: Comparison of schizophrenia, schizoaffective disorder, and mood disorder with psychotic features

Individuals with schizophrenia have significant deficits in premorbid social and academic adjustment compared to individuals with non-psychotic diagnoses. However, it is unclear how severity and developmental trajectory of premorbid maladjustment compare across psychotic disorders. This study examined the association between premorbid functioning (in childhood, early adolescence, and late adolescence) and psychotic disorder diagnosis in a first-episode sample of 105 individuals: schizophrenia (n=68), schizoaffective disorder (n=22), and mood disorder with psychotic features (n=15). Social and academic maladjustment was assessed using the Cannon-Spoor Premorbid Adjustment Scale. Worse social functioning in late adolescence was associated with higher odds of schizophrenia compared to odds of either schizoaffective disorder or mood disorder with psychotic features, independently of child and early adolescent maladjustment. Greater social dysfunction in childhood was associated with higher odds of schizoaffective disorder compared to odds of schizophrenia. Premorbid decline in academic adjustment was observed for all groups, but did not predict diagnosis at any stage of development. Results suggest that social functioning is disrupted in the premorbid phase of both schizophrenia and schizoaffective disorder, but remains fairly stable in mood disorders with psychotic features. Disparities in the onset and time course of social dysfunction suggest important developmental differences between schizophrenia and schizoaffective disorder.     

Depression and anxiety among mothers who bring their children to a pediatric mental health clinic

OBJECTIVE: Maternal psychiatric illness is a potent risk factor for child psychiatric disorders, but little is known about rates of psychiatric diagnoses among mothers who bring their children to pediatric mental health clinics. This study investigated rates of psychiatric disorders among mothers of children presenting for psychiatric evaluation and examined the relationship between maternal diagnosis and child psychopathology. METHODS: Interviewers conducted structured diagnostic interviews with nonpsychotic, school-age children and their mothers (N=222) and collected self-report measures of symptoms, functioning, and social support. RESULTS: One-hundred-thirty-five participating mothers (61 percent) met DSM-IV criteria for a current axis I disorder, most commonly depression (35 percent) and anxiety (42 percent). Children of mothers with a diagnosis met criteria for significantly more diagnoses on the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Lifetime version and had significantly higher scores on measures of internalizing and externalizing symptoms than children of mothers without a diagnosis. Two-thirds of mothers with a diagnosis were not receiving psychiatric treatment. CONCLUSIONS: More than half the mothers who brought their children for psychiatric treatment were themselves suffering from a psychiatric disorder. Maternal psychiatric illness was, in turn, associated with greater occurrence of psychopathology among offspring, underscoring the importance of developing interventions that address the needs of both children with psychiatric disorders and their at-risk mothers.     

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients’ children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

     

Smooth pursuit eye movements in schizophrenia and attentional dysfunction: adults with schizophrenia, ADHD, and a normal comparison group.

BACKGROUND: Smooth pursuit eye movement (SPEM) abnormalities are found in schizophrenia. These deficits often are explained in the context of the attentional and inhibitory deficits central to schizophrenia psychopathology. It remains unclear, however, whether these attention-associated eye movement abnormalities are specific to schizophrenia or are a nonspecific expression of attentional deficits found in many psychiatric disorders. Adult attention-deficit/hyperactivity disorder (ADHD) is an alternative disorder with chronic attentional and inhibitory dysfunction. Thus, a comparison of SPEM in adult schizophrenia and adult ADHD will help assess the specificity question. METHODS: SPEM is recorded during a 16.7 degrees per second constant velocity task in 17 adults with ADHD, 49 adults with schizophrenia, and 37 normal adults; all groups included individuals between ages 25-50 years. RESULTS: Smooth pursuit gain and the frequency of anticipatory and leading saccades are worse in schizophrenic subjects, with normal and ADHD subjects showing no differences on these variables. CONCLUSIONS: Many attention-associated SPEM abnormalities are not present in most subjects with ADHD, supporting the specificity of these findings to the attentional deficits seen in schizophrenia.     

Update on Mental Health of Infants and Children of Parents Affected With Mental Health Issues

This paper highlights the most recent publications, in the field of psychiatry, on offspring of patients with psychiatric illnesses such as schizophrenia and bipolar disorder, and then summarizes what we know about the progeny of adults with mood disorders, the most prevalent of parental disorders. Studies examining personality disorders and contextual factors such as stress and trauma are examined with a focus on the crucial question of development and attachment status in children. Findings converge to reveal that offspring of parents (generally mothers) with most major psychiatric disorders present a higher risk for all mental disorders, and a wide range of disorders are also found in children, adolescent, and finally adult offspring of mothers with mood and anxiety disorders. Developmental psychopathology and infant and child psychiatry have focused on early relationship formation through social interaction and attachment patterns as pathways affected by vulnerability or resilience factors. First year of life longitudinal studies following mothers and infants has shown that maternal psychopathology is positively correlated with higher risk of attachment issues. It would seem that pathology appears when adaptation to real-life contexts becomes difficult in association with an accumulation of negative individual characteristics and environmental circumstances. We suggest that in order to move forward psychiatry should embrace a developmental cascade model, which posits a cumulative pathway for the emergence of psychopathology in the developing child. We propose that we have sufficient knowledge today to start implementing multilevel approaches to enhance the health and mental health of the next generation.     

Evaluation of the Appropriateness of Multiple Symptom Validity Indices in Psychotic and Non-Psychotic Psychiatric Populations

Although it is recognized that significant cognitive deficits are inherent in many psychiatric disorders, there is minimal research on whether the deficits can cause a failing score on symptom validity tests (SVTs). The performances of 104 and 178 patients with psychotic disorders and non-psychotic psychiatric disorders, respectively, on seven SVTs were examined. Analyses indicate that most of these SVTs have specificity rates of 90% or better for both clinical groups. Further, only 7% of patients in the psychotic group and 5% of patients in the non-psychotic psychiatric group produced false-positive classifications based on malingering criteria similar to those suggested by Slick et al. (i.e., failure of two or more SVTs or failure of one SVT at statistically significantly worse than chance rates). Consequently this research indicates that psychiatric disorders typically do not adversely affect SVT performance.     

Evaluation of the appropriateness of multiple symptom validity indices in psychotic and non-psychotic psychiatric populations

Although it is recognized that significant cognitive deficits are inherent in many psychiatric disorders, there is minimal research on whether the deficits can cause a failing score on symptom validity tests (SVTs). The performances of 104 and 178 patients with psychotic disorders and non-psychotic psychiatric disorders, respectively, on seven SVTs were examined. Analyses indicate that most of these SVTs have specificity rates of 90% or better for both clinical groups. Further, only 7% of patients in the psychotic group and 5% of patients in the non-psychotic psychiatric group produced false-positive classifications based on malingering criteria similar to those suggested by Slick et?al. (i.e., failure of two or more SVTs or failure of one SVT at statistically significantly worse than chance rates). Consequently this research indicates that psychiatric disorders typically do not adversely affect SVT performance.