Prospective study of adult mental disturbance in offspring of women with psychosis

BACKGROUND: The high-risk method is an important strategy for studying the antecedents and causes of schizophrenia and other psychoses. The Swedish High-Risk Project is a prospective longitudinal study of offspring of women with a history of schizophrenic, schizoaffective, affective, or unspecified functional psychoses and control women with no history of psychosis. The offspring and their environments were studied beginning before birth, and again during childhood. This article reports the mental outcome results from the first adult follow-up at age 22 years. METHODS: Of 178 offspring, 166 (93%) were followed up and blindly assessed using standardized methods, including a self-report scale for mental symptoms and the Structured Clinical Interview for DSM-III-R. RESULTS: Compared with controls (n = 91), the offspring of mothers with schizophrenia (n = 28) showed a significantly increased frequency of DSM-III-R Axis I and Axis II disorders, poor global functioning, high Symptom Checklist-90 scores, and a history of mental health care and psychopharmacologic medication use. Offspring of mothers with affective disorders (n = 22) showed high Symptom Checklist-90 scores, more frequent poor functioning, and receipt of mental health care, with a significant increase in Axis I depressive disorders and no increase in Axis II disorders. The extension of schizophrenia and affective risk groups to include additional maternal "spectrum cases" (10 and 15 individuals, respectively) generally yielded similar results. CONCLUSIONS: Maternal schizophrenia is associated with widespread increases in offspring mental disturbance in adolescence and young adulthood, differing from offspring disturbance associated with maternal affective disorder.     

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.     

Prospective study of adolescents with subsyndromal psychosis: characteristics and outcome

OBJECTIVE: The aim of this study was to examine the characteristics and outcome of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities. METHODS: As part of an ongoing, naturalistic study investigating adolescents considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/- 2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS: Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up data developed schizophrenia or schizoaffective disorder, and only 2 subjects (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other diagnoses at follow-up were mood disorders (34.6%), personality disorders (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome, 38.5% of the patients progressed to a syndromal psychotic disorder, 23.1% continued to have attenuated positive symptoms, and 38.4% improved to having attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was associated with lower maximum levels of negative symptoms (p = 0.02) and higher likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic mood disorder are unreliable predictors of a syndromal psychotic disorder outcome at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where these disorders fall in the developmental course of schizophrenia.     

Neuropsychological impairment and its neurological correlates in adult offspring with heightened risk for schizophrenia and affective psychosis

OBJECTIVE: Schizophrenia is generally considered to be a neurodevelopmental disorder reflected in findings of neuropsychological impairments and neurological abnormality in patients and their relatives. The authors investigated whether neuropsychological impairments are related to neurological abnormality and whether such deficits also characterize risk for affective psychosis. METHOD: In a longitudinal study with a 93% rate of effective follow-up, the authors investigated neuropsychological impairment and its relation to neurological abnormality at a mean age of 22.3 years in 74 offspring of mothers with a history of psychotic disorders (38 offspring with heightened risk for schizophrenia and 36 with risk for affective psychosis) and 88 normal-risk offspring born to mothers with no history of psychosis. RESULTS: Offspring with genetically heightened risk for schizophrenia showed significantly impaired verbal memory, selective attention, and grammatical reasoning, compared with normal-risk offspring. Having impaired verbal memory, attention, and grammatical reasoning functions identified a significantly larger subgroup (16%) among offspring with heightened risk for schizophrenia than among offspring with heightened risk for affective psychosis (0%) and among normal-risk offspring (3%). Multiple neuropsychological functions were significantly related to neurological abnormality in offspring with heightened risk for schizophrenia and in normal-risk offspring but not among offspring with heightened risk for affective psychosis. The extension of schizophrenia and affective psychosis risk groups to include additional offspring of mothers with psychosis-spectrum disorders yielded results similar to those for the core risk groups. CONCLUSIONS: The neurocognitive dysfunction attending heightened risk for schizophrenia is likely based on genetically mediated neurodevelopmental factors, with schizophrenia and affective psychosis belonging to different biological spheres.     

High-risk children in young adulthood: a longitudinal study from birth to 32 years

The developmental courses of high-risk and resilient children were analyzed in a follow-up study of members of a 1955 birth cohort on the island of Kauai, Hawaii. Relative impact of risk and protective factors changed at various life phases, with males displaying greater vulnerability than females in their first decade and less during their second; another shift appears under way at the beginning of their fourth decade. Certain protective factors seem to have a more general effect on adaptation than do specific risk factors.     

Educational attainment in offspring bereaved by sudden parental death from external causes: a national cohort study from birth and throughout adulthood

Social Psychiatry and Psychiatric Epidemiology - Previous research has linked loss of a parent during childhood to reduced educational aspirations, school performance, and educational attainment...     

Quality of early mother-child interaction associated with depressive psychopathology in the offspring: a prospective study from infancy to adulthood

Evidence from animal research has revealed that less maternal care results in disturbed emotionality in the offspring. In the present study, the long-term impact of maternal responsiveness and stimulation during early mother–child interaction on depressive psychopathology was examined until adulthood. Data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness and stimulation as well as infant responsiveness were evaluated by trained raters. At age 19 years, 314 participants (145 males, 169 females) were characterized on measures of depression through interview and questionnaire. In addition, measures of depression and anxiety were available from assessments in childhood. Results indicated that less maternal stimulation during early interaction was associated with a higher risk of depression in the offspring until the age of 19 years. In addition, children of less stimulating mothers showed more depressive symptoms at age 19 years and displayed more anxiety and depressive symptoms between the ages of 4.5 and 15 years. In contrast, maternal responsiveness was unrelated to children’s outcome. In accordance with findings from animal research, the present study provides first longitudinal evidence in humans of a continuous and long-term influence of early maternal interaction behavior on the offspring’s psychological adjustment until adulthood. The results suggest that the amount of maternally initiated contact behavior in a very early developmental stage may be crucial for children’s mental health, regardless of child and maternal responsiveness.     

Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease

We prospectively evaluated the clinical and biochemical responses to enzyme-replacement therapy (ERT) with macrophage-targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5–8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher cells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain–CSF compartment in some patients.     

Further evidence that congenital dermatoglyphic abnormalities are associated with psychosis: a twin study

The presence of abnormal palmar flexion creases (APFC) and dermatoglyphic ridge dissociation (RD) may constitute enduring evidence of a prenatal insult that occurred before the third trimester of intrauterine life. We examined these dermatoglyphic abnormalities in a twin study of psychotic disorders. RD and APFC were analyzed in a monozygotic (MZ) twin sample from the Maudsley Hospital in London (11 normal control pairs, 16 pairs concordant for psychosis, 9 pairs discordant for psychosis, 1 concordant triplet, and 1 triplet with one affected member). The risk of either RD or APFC was 44 percent in affected twins and 20 percent in nonaffected twins (odds ratio = 3.25, 95% confidence interval: 1.03-10.31; one-sided p = 0.023). In the group of MZ twins discordant for psychosis, discordance for RD or APFC always paralleled discordance for psychosis (one-sided p = 0.078), suggesting the operation of nongenetic factors. The results confirm previous work suggesting the possibility that nongenetic factors early in pregnancy contribute to the liability to develop psychosis in later life.     

Childhood behavior problems linked to sexual risk taking in young adulthood: a birth cohort study

OBJECTIVE: To study whether behavioral and emotional problems during childhood predicted early sexual debut, risky sex at age 21 years, and sexually transmitted infections up to age 21 years. Some possible mediational pathways were also explored. METHOD: Participants were enrolled in the Dunedin Multidisciplinary Health and Development Study (n = 1,037), a prospective, longitudinal study of a New Zealand birth cohort born in 1972-1973. Data obtained at ages 5, 7, 9, 11, 13, 15, and 21 years were used. Adjustment was made for gender, socioeconomic status, parenting factors, and residence changes. RESULTS: High levels of antisocial behavior between age 5 and 11 years were associated with increased odds of early sexual debut (adjusted odds ratio [AOR] 2.17, 95% confidence [CI] 1.34-3.54) and risky sex (AOR 1.88, 95% CI 1.04-3.40). No relationship was observed between hyperactivity and later sexual health outcomes. In contrast, high levels of anxiety were associated with reduced odds of risky sex (AOR 0.45, 95% CI 0.25-0.80) and sexually transmitted infections (AOR 0.34, 95% CI 0.17-0.70). Involvement with delinquent peers explained some of the association between antisocial behavior and early sexual debut and risky sex. A poor relationship with parents also explained some of the association between antisocial behavior and early sexual debut. CONCLUSIONS: The findings demonstrate links between behavioral and emotional problems occurring early in life and later deleterious sexual health outcomes. Targeting antisocial behavior and teaching accurate appraisals of danger during childhood may help mitigate these negative consequences.     

Xeroderma pigmentosum with neurological abnormalities. A clinical and neuropathological study

A clinical and neuropathological study of a case of xeroderma pigmentosum with severe neurological abnormalities was performed. The patient developed sensitivity to the sun, followed by freckles and malignant skin tumors. Some years after the onset of the cutaneous symptoms, a slowly progressive mental deterioration was noted. Subsequently, dysarthria, increased sensitivity and a tendency to cry and to be easily frightened developed together with ataxia and spasticity of the limbs. Late in the course of the disease the patient was severely disabled because of spastic tetraplegia. The clinical examination revealed generalized slowing in EEG, mixed sensory and motor neuropathy in EMG, thick skull, both cerebral cortical atrophy and ventricular dilatation in computed tomography and marked decrease in cerebrospinal homovanillic acid content. The neuropathological study showed marked loss of neurons in the basal nucleus of Meynert, the substantia nigra, the cerebellum, medulla and spinal cord. Diffuse loss of neurons was noted in the cerebral cortex and in the deep cerebral nuclei. In the nerve cells, a high amount of cytoplasmic lipofuscin was observed in some areas of CNS. The sciatic nerve showed marked loss of axons and heavy deposition of collagen around the remaining nerve fibers. The present neuropathological findings explain many of the clinical symptoms observed in xeroderma pigmentosum and show similarities with those observed in olivopontocerebellar atrophy, although the basic mechanism for the CNS damage is still unclear.     

Malformations in offspring of 305 epileptic women: a prospective study

This paper deals with malformations detected in 26 of 315 newborns of 305 epileptic mothers followed prospectively. In 3 more cases, malformations were detected in utero and therapeutic abortion was performed. Two hundred and seven women were on monotherapy, 102 on polytherapy and 9 were not treated. In total, malformations overall incidence was 9.1%. Minor anomalies were detected in 42 newborns (13.3%). A higher rate of malformations and minor anomalies was found among offspring of mothers treated with valproic acid (VPA). In the VPA group, mothers of malformed babies had higher plasma levels in the first trimester than mothers of babies without malformations. The need for accurate prenatal diagnostic studies in pregnant women with epilepsy is stressed.     

Comparative study of neurological soft signs in schizophrenia with onset in childhood, adolescence and adulthood

OBJECTIVE: To compare neurological soft signs (NSS) in patients of schizophrenia with onset in childhood (COS), adolescence (AdOS) and adulthood (AOS). METHOD: Assessment of NSS in 15 patients of COS and 20 patients each of AdOS and AOS was made using condensed neuropsychiatric examination for NSS. RESULTS: NSS were significantly more frequent in COS (100%) and AdOS (90%) when compared with AOS (55%) patients. COS patients showed significantly higher scores on temporal and frontal lobe NSS, of which differences between the three groups in temporal lobe NSS disappeared on ancova. Parietal lobe dependent NSS were seen in a few COS patients. The NSS were more in those with lesser IQ, lower education and higher Positive and Negative Syndrome Scale scores. CONCLUSION: Findings indicate that earlier onset types may be more strongly associated with a generalized disruption of brain function. Non-suppression of primitive reflexes with cortical maturation in COS point towards disordered neurodevelopment. Preponderance of fronto-temporal and a relative lack of parietal lobe NSS point towards differential lobar involvement. Neurodevelopmental abnormalities leading to NSS also lead to lower IQ and lower educational level.     

Neurotrophins in murine viscera: a dynamic pattern from birth to adulthood

There is growing evidence that target-derived neurotrophins regulate the function of visceral neurons after birth. However, the postnatal profile of neurotrophin supply from internal organs is poorly described. In this study, we compared neurotrophin concentrations in lysates of murine peripheral target tissues (lung, heart, liver, colon, spleen, thymus, kidney and urinary bladder) at different time points after birth. In most organs, there was a decrease of neurotrophin concentrations in the first weeks after birth. In contrast, there were characteristic increases of specific neurotrophins during adolescence or adulthood. These increases were found for nerve growth factor (NGF) in the heart, thymus, kidney and liver, for brain-derived neurotrophic factor (BDNF) in the lung, and for neurotrophin-3 (NT-3) in the colon. In conclusion, we show that neurotrophins display a very differential and dynamic profile in internal organs after birth.     

Relationship of neurological abnormalities in schizophrenics to family psychopathology

Competing etiological models make opposite predictions as to the relationship between focal neurological abnormalities in schizophrenics and the prevalence of psychosis in their families. In previous studies of neurological abnormalities in schizophrenia, the authors found an increased prevalence of focal neurological signs in both patients and their nonschizophrenic relatives. The current study examines the relationship between neurological abnormalities in 24 schizophrenic patients and psychopathology in their families. A family history of psychotic psychopathology was found to be associated with an increased prevalence of focal neurological abnormalities in the schizophrenics. The results are relevant to current models of the potential role of neurological factors in the etiology of schizophrenia and illustrate how family studies of the joint distribution of psychiatric and neurological data can potentially help to distinguish between different etiological models.     

Metabolic abnormalities in an early psychosis service: a retrospective, naturalistic cross-sectional study

Aim: There is an increasing recognition of the impact of weight gain on the development of metabolic abnormalities in young people receiving atypical antipsychotic drugs for first‐episode psychosis. This study examined the prevalence of such abnormalities in a specialist early‐intervention community mental health team. Methods: A retrospective case record audit of 85 patients 16–27 years old attending the Early Psychosis Service between October 2006 and June 2008, who had at least one metabolic measure defined as: weight, body mass index (BMI), waist circumference, blood pressure, and fasting blood glucose and lipids. Metabolic syndrome identified by the International Diabetes Federation (IDF) criteria. Results: Fifty‐five percent of males and 42% of females were overweight or obese at a median treatment duration of 8 months. Duration of antipsychotic therapy was associated with higher BMI (r = 0.28, P < 0.01). More than 40% of the total sample had high waist circumference. Of the 64 subjects with complete metabolic data, eight (12.5%) met full IDF criteria for metabolic syndrome, and another 21 (32.8%) had either increased waist with one metabolic abnormality or normal waist and two metabolic abnormalities. Conclusion: Over a third of young patients being treated for their first episode of psychosis either had metabolic syndrome or showed metabolic abnormalities. Treatment duration related to higher BMI and greater prevalence of metabolic syndrome. Detection of metabolic complications after treatment instigation in patients with first‐episode psychosis will permit early intervention with lifestyle or drug interventions in those at risk of significant physical health morbidity.