Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder

This study examined the relation between childhood ocular alignment deficits and adult psychiatric outcomes among children at high-risk for schizophrenia and controls. A sample of 265 Danish children was administered a standardized eye exam assessing strabismus and related ocular alignment deficits. All children whose mothers or fathers had a psychiatric diagnosis of schizophrenia comprised the first group (N=90). Children who had at least one parent with a diagnosis other than schizophrenia comprised the first matched control group (N=93). The second control group consisted of children with no parental diagnoses (N=82). In 1992, adult psychiatric outcome data were obtained for 242 of the original subjects. It was found that children who later developed a schizophrenia-spectrum disorder had significantly higher eye exam scale and strabismus scale scores compared to children who developed other non-psychotic psychopathology and children who did not develop a mental illness. The mean rank for children in the high-risk group (offspring of parents with schizophrenia) on the eye scale and the strabismus scale was greater than the mean rank for children in the matched control groups (both offspring of parents with other non-psychotic disorder and no mental illness), although the results failed to reach statistical significance. Results from this study suggest a premorbid relation between ocular deficits and schizophrenia-spectrum disorders in childhood prior to onset of psychopathology in adulthood. Strabismus may serve as a premorbid marker for spectrum disorders and may have implications for the understanding of early aberrant neurological development related to later schizophrenia-spectrum disorders.     

Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study

In vivo (31)P magnetic resonance spectroscopy ((31)P MRS) studies have shown abnormal membrane phospholipid metabolism in the prefrontal cortex (PF) in the early course of schizophrenia. It is unclear, however, whether these alterations also represent premorbid risk indicators in schizophrenia. In this paper, we report in vivo (31)P MRS data on children and adolescents at high risk (HR) for schizophrenia. In vivo (31)P MRS studies of the PF were conducted on 16 nonpsychotic HR offspring of parents with schizophrenia or schizoaffective disorder, and 37 age-matched healthy comparison (HC) subjects. While 11 of the HR subjects had evidence of Axis I psychopathology (HR-P), five HR subjects had none (HR-NP). We quantified the freely mobile phosphomonoester (PME) and phosphodiester (PDE) levels reflecting membrane phospholipid precursors and breakdown products, respectively, and the relatively broad signal underlying PDE and PME peaks, comprised of less mobile molecules with PDE and PME moieties (eg, synaptic vesicles and phosphorylated proteins). Compared to HC subjects, HR subjects had reductions in freely mobile PME; the differences were accounted for mainly by the HR-P subjects. Additionally, HR-P subjects showed increases in the broad signal underlying the PME and PDE peaks in the PF. To conclude, these data demonstrate new evidence for decreased synthesis of membrane phospholipids and possibly altered content or the molecular environment of synaptic vesicles and/or phosphoproteins in the PF of young offspring at risk for schizophrenia. Follow-up studies are needed to examine the predictive value of these measures for future emergence of schizophrenia in at-risk individuals.     

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.     

Psychopathology in offspring from multiplex alcohol dependence families with and without parental alcohol dependence: a prospective study during childhood and adolescence

Multiplex families ascertained through multiple alcohol dependent individuals appear to transmit alcohol and drug use disorders at higher rates than randomly selected families of alcoholics. Our goal was to investigate the risk of developing specific psychiatric diagnoses during childhood or adolescence in association with familial risk status (high-risk [HR] or low-risk [LR]) and parental diagnosis. Using a prospective longitudinal design, HR offspring from three generation multiplex alcohol dependence families and LR control families were followed yearly. Data analysis was based on consensus diagnoses from 1738 yearly evaluations conducted with the offspring and a parent using the K-SADS, and separately modeled the effects of familial susceptibility and exposure to parental alcohol dependence. Multiplex family membership and parental alcohol and drug dependence significantly increased the odds that offspring would experience some form of psychopathology during childhood or adolescence, particularly externalizing disorders. Additionally, parental alcohol dependence increased the odds that adolescent offspring would have major depressive disorder (MDD). While it is well known that parental substance dependence is associated with externalizing psychopathology, the increased risk for MDD seen during adolescence in the present study suggests the need for greater vigilance of these children.     

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.     

Attentional and neurocognitive characteristics of high-risk offspring of parents with schizophrenia compared with DSM-IV attention deficit hyperactivity disorder children

Offspring of individuals with schizophrenia are at increased baseline risk for a range of early mental disorders. Studies investigating the premorbid characteristics of individuals with schizophrenia indicate that they suffer from social, behavioral, attentional and neurocognitive impairments, often resembling attention deficit hyperactivity disorder (ADHD). In this study, we compared the executive functioning and general intelligence among three groups: (i) children and adolescents with DSM-IV ADHD (n=41), (ii) "high-risk" (HR) offspring of parents with DSM-IV schizophrenia, and (iii) normal comparison subjects (n=35). Our results indicated that both HR and ADHD groups had lower Verbal IQ scores. ADHD cases had significantly lower percent correct and total errors in Wisconsin Cart Sorting Test when compared with normal comparison subjects. The HR cases also had lower Performance IQ scores as well as worse abstraction--flexibility and comprehension performance. The HR group was further stratified with (HR-A) and without (HR-NA) comorbid ADHD, and HR-A subjects were significantly noted to be more impaired on most tests. The overall worse performance of HR offspring was attributable to significantly lower performance among the HR-A youth. Further, our results suggested that the most profoundly impaired HR subjects were in fact children and adolescents who also met criteria for ADHD. Future studies with broader neuropsychological test batteries are necessary to investigate the differences and similarities between ADHD and the HR-A subgroup.     

Adverse outcomes associated with personality disorder not otherwise specified in a community sample

OBJECTIVE: The authors investigated 1) whether adolescents and adults in the community diagnosed with personality disorder not otherwise specified are at elevated risk for adverse outcomes, and 2) whether this elevation in risk is comparable with that associated with the DSM-IV cluster A, B, and C personality disorders. METHOD: A community-based sample of 693 mothers and their offspring were interviewed during the offspring's childhood, adolescence, and early adulthood. Offspring psychopathology, aggressive behavior, educational and interpersonal difficulties, and suicidal behavior were assessed. RESULTS: Individuals who met DSM-IV criteria for personality disorder not otherwise specified were significantly more likely than those without personality disorders to have concurrent axis I disorders and behavioral, educational, or interpersonal problems during adolescence and early adulthood. In addition, adolescents with personality disorder not otherwise specified were at significantly elevated risk for subsequent educational failure, numerous interpersonal difficulties, psychiatric disorders, and serious acts of physical aggression by early adulthood. Adolescents with personality disorder not otherwise specified were as likely to have these adverse outcomes as those with cluster A, B, or C personality disorders or those with axis I disorders. CONCLUSIONS: Adolescents and young adults in the general population diagnosed with personality disorder not otherwise specified may be as likely as those with DSM-IV cluster A, B, or C personality disorders to have axis I psychopathology and to have behavioral, educational, or interpersonal problems that are not attributable to co-occurring psychiatric disorders. Individuals with personality disorder not otherwise specified and individuals with DSM-IV cluster A, B, or C personality disorders are likely to be at substantially elevated risk for a wide range of adverse outcomes.     

MMPI measures as signs of predisposition to mental disorder among adoptees at high risk for schizophrenia

The DSM-III-R diagnoses of a group of adoptees were predicted by the MMPI (Minnesota Multiphasic Personality Inventory) schizophrenia-related scales in the Finnish Adoptive Family Study. The sample consisted of 60 high-risk (HR) adopted-away offspring of biologic mothers with a diagnosis of broad schizophrenia spectrum and 76 low-risk (LR) control adoptees. They were assessed with the MMPI before the onset of any psychiatric disorder at a mean age of 24 years. High scores on the Psychopathic Deviate scale predicted psychiatric disorder at 11-year follow-up. Furthermore, LR adoptees', but not HR adoptees', mental disorders could be predicted with the MMPI scales Psychopathic Deviate and Golden-Meehl Indicators. These scales measure schizophrenia-related personality traits, including a social behavior, anhedonia, ambivalence, interpersonal aversiveness, and formal thought disturbances.     

Psychometric deviance in offspring at risk for schizophrenia: I. Initial delineation of a distinct subgroup

Psychometric signs from the Minnesota Multiphasic Personality Inventory (MMPI), which measure substantive disturbances in thinking, social relatedness, volition, and affective expressivity, were evaluated as possible indicators of transmissible liability specific to schizophrenia. Children of three criterion groups in the New York High-Risk Project--offspring at high risk (HR) for schizophrenia, psychiatric comparison (PC) offspring at risk for affective disorders, and normal comparison (NC) offspring not at augmented risk for psychiatric morbidity--were tested before the expression of schizophrenic psychopathology, when the subjects ranged in age from 13 to 26 years. The rate of psychometric deviance in the HR group (23%) was significantly higher than that in either the PC (7%) or NC (2%) groups, and profile analyses showed that the HR subgroup could be delineated by qualitative distinctions in personality functioning. Our results support the utility of MMPI indicators in etiologic investigations of schizophrenia.     

Relationship between psychiatric disorders and sexually transmitted diseases in a nationally representative sample

Objective

Sexually transmitted diseases (STDs) are a significant public health concern. Numerous internalizing and externalizing psychiatric disorders have been found to be related to STD risk. However, to date, no studies have examined several psychiatric disorders simultaneously to account for STD risk. Given that psychiatric disorders often co-occur and can be explained by a limited number of latent dimensions of psychopathology, it is important to examine whether the relationship between STDs and psychiatric disorders is best explained by broad dimensions of psychopathology.

Methods

The current study examined the associations between a range of Axis I and II psychiatric disorders at baseline and rates of STDs at a three-year follow-up in a large, nationally representative sample of adults in the United States (n = 34,434). A confirmatory factor analysis (CFA) was conducted to fit three factors, two internalizing and one externalizing. Structural equation modeling (SEM) was used to assess the relationships between and among the factors and STD status and to test for mediation.

Results

In bivariate analyses, most Axis I and Axis II disorders were associated with STD diagnosis at Wave 2, whereas the results of the structural model showed that only the externalizing factor was significantly associated with STD diagnosis at Wave 2. Further, the externalizing factor mediated the relationship between one of the internalizing factors and STD diagnosis.

Conclusion

Findings suggest the unique contribution of externalizing psychopathology to STD risk and the importance of examining latent dimensions of disorders when understanding this relationship between psychiatric disorders and STDs.     

Schizotypal personality traits in Gilles de la Tourette syndrome

OBJECTIVES: Gilles de la Tourette syndrome (GTS) is a chronic tic disorder associated with comorbid psychopathology, including obsessionality, affective instability and attention-deficit hyperactivity disorder. Evidence linking GTS with schizophrenia-like symptoms is limited and equivocal, despite a common putative substrate involving dopaminergic dysfunction within frontostriatal circuits. The aim of this study was to quantify the prevalence of schizotypal traits in GTS and to detail the relationship between schizotypy and comorbid psychopathology. MATERIALS AND METHODS: A total of 102 subjects with GTS were evaluated using the Schizotypal Personality Questionnaire and standardized neurological and psychiatric rating scales. The predictive interrelation between schizotypy, tic-related symptoms and psychiatric comorbidities was investigated using correlation and multiple regression analyses. RESULTS: In our clinical population, 15% of the subjects were diagnosed with the schizotypal personality disorder according to the DSM-IV criteria. The strongest predictors of schizotypy were obsessionality and anxiety ratings. The presence of multiple psychiatric comorbidities correlated positively with schizotypy scores. CONCLUSIONS: Schizotypal traits are relatively common in patients with GTS, and reflect the presence of comorbid psychopathology, related to the anxiety spectrum. In particular, our preliminary results are consistent with a shared neurochemical substrate for the mechanisms underpinning tic expression, obsessionality and specific schizotypal traits.     

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.     

Mortality risk among offspring of psychiatric inpatients: a population-based follow-up to early adulthood

OBJECTIVE: The purpose of this article was to estimate relative risks of all-cause mortality associated with parental psychiatric disorder based on offspring age (up to 25 years of age), parental diagnosis, maternal versus paternal disorder, and number of affected parents. METHOD: The study group consisted of all Danish singleton live and stillbirths (N=1.46 million) during 1973-1998, identified using the Central Population Register and Medical Birth Register. Dates of death were recorded with follow-up to Jan. 1, 1999. Parental admission histories since 1969 were obtained from the Psychiatric Central Register. RESULTS: Mortality risks were elevated from birth through early adulthood among offspring of people admitted with any type of psychopathology, although relative risks were attenuated during school attendance years. Effect sizes varied according to offspring ages, the highest being during infancy. The following high-risk subgroups were identified: postneonates with two mentally ill parents, neonates and postneonates whose mothers had alcohol and drug-related disorders, and neonates whose mothers had affective disorders. In general, from the postneonatal period onward, there was no indication that maternal psychopathology is associated with higher offspring mortality risk than paternal disorder. CONCLUSIONS: The greatest number of excess deaths were attributable to alcohol-related disorders, this being the most prevalent paternal diagnostic category and the second most prevalent in mothers. Some findings were unexpected. For example, there was no evidence that mortality risk among offspring of parents with schizophrenia and related disorders was significantly greater than that associated with all other parental psychiatric conditions, whereas the relative risk for neonatal death associated with maternal affective disorders was markedly raised.     

Psychopathology in the offspring of parents with bipolar disorder: a controlled study.

BACKGROUND: To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psychiatric disorders in these youth. METHODS: Using structured diagnostic interviews (Structured Clinical Interview for DSM-IV [SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. RESULTS: Compared with offspring of parents without mood disorders, high-risk youth had elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also had significantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. CONCLUSIONS: These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk for subsequent bipolar disorder in high-risk samples.     

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.     

Stability of Thought Disorder Index among high-risk and low-risk adoptees in the Finnish adoptive family study of schizophrenia.

The aim of the study was to evaluate whether thought disorders are stable, trait-like features specific to subjects who have a genetic liability to schizophrenia or a psychiatric disorder. The thought disorders of adoptees genetically at high risk (HR) or low risk (LR) for schizophrenia from the Finnish adoptive family study of schizophrenia were evaluated twice at a mean interval of 11 years, using the sum of the Thought Disorder Index (TDI) scores on the Rorschach (TD(R)). At the initial assessment, the mean TD(R) scores of women were significantly higher than those of men, while no association between genetic risk and psychiatric status or their interactions with the TD(R) scores at baseline were found. The main finding was that the initial TD(R) scores statistically significantly predicted the TD(R) scores at follow-up, thus indicating the stability of thought disorder over time. However, neither genetic or psychiatric status nor gender or any interaction between these variables associated with TD(R) at follow-up.     

Diagnosis of personality disorders by the Millon Clinical Multiaxial Inventory

The diagnostic efficiency of the Millon Clinical Multiaxial Inventory (MCMI) was examined with regard to the diagnosis of DSM-III axis II personality disorders by practicing psychiatrists. The MCMI displayed fairly good sensitivity but poor specificity and predictive power regarding the diagnosis of any personality disorder. Two possible explanations were offered: a) axis I psychopathology inflates scores on the MCMI personality disorder scales and causes an overdiagnosis of personality disorders by the test; or b) there is an under-recognition of axis II personality disorders (especially in the context of obvious axis I psychopathology) by the average practicing clinician.     

Parents with bipolar disorder: Are disease characteristics good predictors of psychopathology in offspring?

PurposeTo investigate rates of psychopathology in the offspring of subjects with bipolar disorder (BP-offspring) compared to the offspring of healthy subjects (HC-offspring) in a Spanish sample and to study possible predictors of psychopathology in BP-offspring.SubjectsFifty BP-offspring from 36 families and 25 HC-offspring from 25 families.MethodsPsychopathology was compared in BP-offspring and HC-offspring. Factors associated with DSM-IV axis I disorders in BP-offspring were analyzed using logistic regression.ResultsHalf of BP-offspring fulfilled the diagnostic criteria for at least one axis I disorder with attention-deficit/hyperactivity disorder (30%), anxiety disorders (14%) and affective disorders (10%) as the most frequent. After controlling for having more than one sibling in the study, the odds ratio for BP-offspring presenting an axis I disorder was 15.02 when a biological parent had bipolar disorder with a lifetime history of psychotic symptoms and 3.34 when one parent had bipolar II disorder. Moreover, a higher Global Assessment of Functioning score in the biological co-parent was associated with a significantly lower frequency of axis I disorders in BP-offspring.Discussion and conclusionsPsychopathology in BP-offspring should be routinely assessed, with special emphasis on children from parents with specific disease characteristics (psychosis, BP II disorder) in order to establish an early diagnosis and appropriate interventions.