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T D Cannon

Publications and source records attributed to T D Cannon.

At least 19 recordsLinked to original sources
PubMed2006

Infant motor development is associated with adult cognitive categorisation in a longitudinal birth cohort study.

BACKGROUND: The relationship between the age of reaching infant developmental milestones and later intellectual function within the normal population remains unresolved. We hypothesised that the age of learning to stand in infancy would be associated with adult executive function and that the association would be apparent throughout the range of abilities, rather than confined to extremes. METHODS: The Northern Finland 1966 Birth Cohort is based upon 12,058 live-born children in a geographic and temporally defined population. Information on age at learning to stand without support was obtained at one year. At age 33-35 a random sample of 104 subjects underwent a neuropsychological test battery including tests of executive function (cognitive categorisation), visuo-spatial memory, verbal learning and visual object learning. We investigated associations between developmental data and adult neuropsychological test scores. RESULTS: There was a significant linear relationship between age of learning to stand and adult categorisation: the earlier the attainment of the milestone, the better was the categorisation. No such relationships were observed between infant neurodevelopment and adult cognition in other neuropsychological domains. CONCLUSION: Even within the normal range of development, early development in the gross motor domain is associated with better adult executive function (in tests of categorisation). Investigation of the determinants and sequelae of normal neural development will facilitate research into a variety of neurodevelopmental disorders.

Adult↗
PubMed2005

Infant motor development and adult cognitive functions in schizophrenia.

BACKGROUND: Childhood neuromotor dysfunction is a risk factor for schizophrenia, a disorder in which cognitive deficits are prominent. The relationship between early neurodevelopment and adult cognition in schizophrenia remains unclear. METHODS: We examined the associations between infant motor development and adult cognitive functions in schizophrenia (n = 61) and the general population (n = 104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on ages of learning to stand and walk with or without support were obtained at age 12 months by health visitor assessment. Neurocognitive measures at age 33-35 included executive function, verbal and visual episodic memory, and visuo-spatial working memory. RESULTS: The schizophrenia group achieved neuromotor milestones later and performed significantly worse than the control group on all measures of cognition. In pooled analyses there were associations between infant motor development and adult cognition in the domains of executive function, verbal learning and visuospatial working memory, but not in visual object learning. The pattern of associations between development and cognition was similar in schizophrenia and the general population. CONCLUSIONS: These findings are consistent with the hypothesis that in schizophrenia mild infant motor developmental delay and adult cognitive deficits (at least in some domains) are age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome.

Adult↗
PubMed2005

A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia.

We have previously reported evidence of linkage and association between markers on 1q42 and schizophrenia in a study sample of 498 multiply affected Finnish nuclear families, leading to the recent identification of four significantly associated haplotypes that specifically implicate the Translin-Associated Factor X (TRAX) and Disrupted in Schizophrenia 1 and 2 (DISC1 and DISC2) genes in the genetic etiology of schizophrenia. Previously, the DISC genes were found to be disrupted by a balanced translocation (1;11)(q42.1;q14.3) that cosegregated with schizophrenia and related disorders in a large Scottish pedigree. Interestingly, we also reported earlier suggestive linkage between endophenotypic quantitative traits of visual and verbal memory and microsatellite markers in close proximity to TRAX/DISC, on 1q41. Here, we tested if the identified allelic haplotypes of TRAX/DISC would be associated with visual and/or verbal memory function impairments that are known to aggregate with schizophrenia in families. One haplotype of DISC1, HEP3, displayed association with poorer performance on tests assessing short-term visual memory and attention. Analysis of affected and unaffected offspring separately revealed that both samples contribute to the observed association to visual working memory. These results provide genetic support to the view that the DISC1 gene contributes to sensitivity to schizophrenia and associated disturbances and affects short-term visual memory functions. This finding should stimulate studies aiming at the molecular characterization of how the specific alleles of DISC1 affect the visual memory functions and eventually participates in the development of schizophrenia.

Aged↗
PubMed2002

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗
PubMed2001

Quantitative neural indicators of liability to schizophrenia: implications for molecular genetic studies.

While schizophrenia is substantially heritable, the disorder's molecular genetic basis remains elusive. These efforts have been hindered by an inability to detect nonclinically-penetrant carriers of the predisposing genes and by uncertainties concerning the nature of the non-genetic influences and the extent of locus heterogeneity. The "endophenotype" approach is an alternative method for measuring phenotypic variation that may facilitate the identification of susceptibility genes in the context of complexly-inherited traits. Here we describe the application of this method to measures of brain structure and function in samples of schizophrenia patients and their non-ill first-degree relatives (siblings and co-twins). Our results suggest that there are likely to be multiple heritable dimensions of the central nervous system pathology in schizophrenia, each under the influence of a partially distinct set of genes, one of which involves disturbances in the structure and functioning of frontal lobe systems involved in working memory and another of which appears to render the brain more susceptible to damage to subcortical systems involved in long-term memory following oxygen deprivation in utero. Measures sensitive to quantitative variation in these dimensions of the central nervous system compromise should allow non-penetrant gene carriers to become informative for genetic linkage and facilitate detection of different genetic loci contributing to discrete aspects of disease liability.

Birth Injuries↗
PubMed2001

The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review.

UNLABELLED: Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord 2001: 3: 106 150. C Munksgaard, 2001 OBJECTIVES: To present a comprehensive review of the existing neuropsychological and neuroimaging literature on bipolar affective disorder. This review critically evaluates two common conceptions regarding the neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, and 2) relative right hemisphere (RH) dysfunction is implicated in bipolar illness patients, supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions. METHODS: The major computerized databases (Medline and PSYCInfo) were consulted in order to conduct a comprehensive, integrated review of the literature on the neuropsychology and neuroanatomy of bipolar disorder. Articles meeting specified criteria were included in this review. RESULTS: In a critical evaluation of the above notions, this paper determines that: 1) while there is little evidence for selective RH dysfunction, significant cognitive impairment may be present in bipolar illness, particularly in a subgroup of chronic, elderly or multiple-episode patients, suggesting a possible toxic disease process, and 2) the underlying functional correlate of these cognitive deficits may be white matter lesions ('signal hyperintensities') in the frontal lobes and basal ganglia, regions critical for executive function, attention, speeded information processing, learning and memory, and affect regulation. While this hypothesized neural correlate of cognitive impairment in bipolar disorder is speculative, preliminary functional neuroimaging evidence supports the notion of frontal and subcortical hypometabolism in bipolar illness. CONCLUSIONS: The etiology of the structural brain abnormalities commonly seen in bipolar illness, and their corresponding functional deficits, remains unknown. It is possible that neurodevelopmental anomalies may play a role, and it remains to be determined whether there is also some pathophysiological progression that occurs with repeated illness episodes. More research is needed on first-episode patients, relatives of bipolar probands, and within prospective longitudinal paradigms in order to isolate disease-specific impairments and genetic markers of neurocognitive function in bipolar disorder.

Adult↗
PubMed2001

Genetic influences on brain structure.

Here we report on detailed three-dimensional maps revealing how brain structure is influenced by individual genetic differences. A genetic continuum was detected in which brain structure was increasingly similar in subjects with increasing genetic affinity. Genetic factors significantly influenced cortical structure in Broca's and Wernicke's language areas, as well as frontal brain regions (r2(MZ) > 0.8, p < 0.05). Preliminary correlations were performed suggesting that frontal gray matter differences may be linked to Spearman's g, which measures successful test performance across multiple cognitive domains (p < 0.05). These genetic brain maps reveal how genes determine individual differences, and may shed light on the heritability of cognitive and linguistic skills, as well as genetic liability for diseases that affect the human cortex.

Adult↗
PubMed2001

The neurocognitive phenotype of the 22q11.2 deletion syndrome: selective deficit in visual-spatial memory.

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome) is associated with a high frequency of learning disabilities. Although previous work has demonstrated that verbal skills are typically better preserved than non-verbal skills on both IQ and academic achievement testing in children with this syndrome, such measures are not sufficiently specific to determine a selective cognitive deficit. As part of an ongoing prospective study of patients with this syndrome, 29 children aged 5-17 with confirmed 22q11.2 deletions were assessed with a comprehensive neuropsychological test battery, including matched tasks of verbal and visuospatial memory. Results indicate that 22q patients displayed a selective deficit in visual-spatial memory, which was mirrored by deficits in arithmetic and general visual-spatial cognition. Further, a dissociation between visual-spatial and object memory was observed, indicating further selectivity of this pattern of deficit, and providing evidence for the dissociability of these components of visual cognition. These results indicate that children with 22q11.2 deletions display a specific neurocognitive phenotype, and suggest that this region of Chromosome 22q11 may harbor a gene or genes relevant to the etiology of nonverbal learning deficits.

Adolescent↗
PubMed2000

The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia.

While genetic influences in schizophrenia are substantial, the disorder's molecular genetic basis remains elusive. Progress has been hindered by lack of means to detect nonpenetrant carriers of the predisposing genes and by uncertainties concerning the extent of locus heterogeneity. One approach to solving this complexity is to examine the inheritance of pathophysiological processes mediating between genotype and disease phenotype. Here we evaluate whether deficits in neurocognitive functioning covary with degree of genetic relationship with a proband in the unaffected MZ and DZ co-twins of patients with schizophrenia. Twin pairs discordant for schizophrenia were recruited from a total population cohort and were compared with a demographically balanced sample of control twin pairs, on a comprehensive neuropsychological test battery. The following four neuropsychological functions contributed uniquely to the discrimination of degree of genetic loading for schizophrenia and, when combined, were more highly correlated within MZ pairs than within DZ pairs, in both discordant and control twins: spatial working memory (i.e., remembering a sequence of spatial locations over a brief delay), divided attention (i.e., simultaneous performance of a counting and visual-search task), intrusions during recall of a word list (i.e., "remembering" nonlist items), and choice reaction time to visual targets. Together with evidence from human and animal studies of mediation of these functions by partially distinct brain systems, our findings suggest that there are multiple independently inherited dimensions of neural deficit in schizophrenia and encourage a search for genes contributing to quantitative variation in discrete aspects of disease liability. On tests of verbal and visual episodic memory, but not on the liability-related measures, patients were more impaired than their own MZ co-twins, suggesting a preferential impact of nongenetic influences on long-term memory systems.

Adult↗
PubMed2000

P300 subcomponent abnormalities in schizophrenia: III. Deficits In unaffected siblings of schizophrenic probands.

BACKGROUND: Reduced P300 amplitude is a robust finding in patients with schizophrenia. In previous investigations, we reported reductions of specific subcomponents of the auditory oddball P300 that were independent of acute symptomatology and persistent over time, consistent with a trait abnormality. To clarify whether these stable deficits represented genetic markers of vulnerability to schizophrenia, event-related brain potentials (ERPs) from patients were compared to those from their own healthy siblings and unrelated control subjects. METHODS: Auditory P300 ERPs were acquired from 11 schizophrenic patients, 12 healthy siblings and 23 matched control subjects. Five P300 subcomponents were identified using current source density measures: frontal, bilateral parietal, and bilateral temporal. RESULTS: Consistent with previous reports, patients had reduced parietal and frontal P300 amplitudes. The healthy siblings of the schizophrenic probands had an isolated reduction of the frontal P300. CONCLUSIONS: Frontal P300 amplitude is a potential endophenotypic marker of genetic vulnerability to schizophrenia in individuals who otherwise show no evidence of clinical symptomatology. Given the functional interpretation of the frontal P300 as a physiological correlate of cognitive orienting, this supports the hypothesis that impairments of the neural substrate underlying attentional mechanisms are selective indicators of genetic susceptibility to schizophrenia in high-risk individuals.

Adult↗
PubMed2000

Working memory constrains abstraction in schizophrenia.

BACKGROUND: Abstraction has long been considered an area of differential cognitive deficit in schizophrenia, primarily because of patients' poor performance on the Wisconsin Card Sorting Test (WCST). Yet, the complexity and multidimensional nature of the WCST increases the likelihood that several different cognitive processes, perhaps mediated by different neural systems, are being tapped. METHODS: In the current study, the Abstraction and Working Memory (AIM) task was designed to disentangle abstraction and working memory so that the effects of each cognitive domain could be independently analyzed. The AIM task and a battery of neuropsychological tests were administered to 62 patients with schizophrenia and 62 matched healthy volunteers. RESULTS: Whereas patients with schizophrenia demonstrated deficits in simple abstraction, they were disproportionately impaired with the addition of a minimal memory requirement. CONCLUSIONS: Group differences on WCST performance appear to be attributable to patients' inability to maintain information over a short delay, before that information is used for more complex cognitive operations.

Adolescent↗
PubMed2000

A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia.

In this study, we examined whether fetal hypoxia and other obstetric complications (OCs) are related to risk for adult schizophrenia; whether such effects are specific to cases with an early age at onset; and whether the obstetric influences depend on, covary with, or are independent of familial risk. Subjects were 72 patients with schizophrenia or schizoaffective disorder; 63 of their siblings not diagnosed with schizophrenia; and 7,941 nonpsychiatric controls, whose gestations and births were monitored prospectively with standard research protocols as part of the National Collaborative Perinatal Project. Adult psychiatric morbidity was ascertained via a longitudinal treatment data base indexing regional public health service utilization, and diagnoses were made by review of all pertinent medical records according to DSM-IV criteria. We found that the odds of schizophrenia increased linearly with increasing number of hypoxia-associated OCs and that this effect was specific to cases with an early age at onset/first treatment contact. There were no relationships between schizophrenia and birth weight or other (prenatal/nonhypoxic) OCs. Siblings of patients with schizophrenia were no more likely to have suffered hypoxia-associated OCs than were nonpsychiatric cohort controls. Because the majority of individuals exposed to fetal hypoxia did not develop schizophrenia, such factors likely are incapable of causing schizophrenia on their own. Together, these findings suggest that hypoxia acts additively or interactively with genetic factors in influencing liability to schizophrenia. We propose a model in which the neurotoxic effects of fetal hypoxia may lead to an earlier onset of psychosis because of premature pruning of cortical synapses.

Adult↗
PubMed2000

Childhood neuromotor dysfunction in schizophrenia patients and their unaffected siblings: a prospective cohort study.

Neuromotor dysfunction is a consistent finding in high-risk and archival studies of schizophrenia, but the sources of this dysfunction and its role in the developmental course of the disorder remain poorly understood. This study examined childhood motor predictors of adult psychiatric outcome in a birth cohort sample (72 patients with schizophrenia or schizoaffective disorder, 63 unaffected siblings, and 7,941 nonpsychiatric controls), evaluated prospectively with neurologic examinations at 8 months, 4 years, and 7 years of age. Deviance on motor coordination measures at 7 years was associated with both adult schizophrenia and unaffected sibling status, suggesting that a cofamilial (and perhaps genetic) factor underlies motor coordination deficits in schizophrenia. Unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status, indicating that these deficits may be specific to those who will develop the clinical phenotype. None of the motor precursors were confined to patients with an early age at first treatment contact. Fetal hypoxia predicted unusual movements at 4 but not 7 years among the preschizophrenia subjects, suggesting neurodevelopmental dependence of its functional effects. Neither prenatal complications nor birth weight were associated with motor dysfunction in preschizophrenia subjects or their unaffected siblings at any age. Finally, preschizophrenia children did not show the expected developmental decline in unusual movements, perhaps reflecting aberrant functional maturation of cortical-subcortical pathways.

Adult↗
PubMed2000

Childhood cognitive functioning in schizophrenia patients and their unaffected siblings: a prospective cohort study.

While it is known that children of schizophrenia parents perform more poorly on tests of cognitive functioning than children of normal parents, less certain is the degree to which such deficits predict schizophrenia outcome, whether cognitive functioning deteriorates during childhood in preschizophrenia individuals, and whether nongenetic etiologic factors (such as obstetric complications) contribute to these deficits. In the present study, 72 patients with schizophrenia or schizoaffective disorder, 63 of their siblings not diagnosed with schizophrenia, and 7,941 controls with no diagnosis were ascertained from a birth cohort whose members had been evaluated with standardized tests of cognitive functioning at 4 and 7 years of age. Adult psychiatric morbidity was ascertained via a longitudinal treatment data base indexing regional public health service utilization, and diagnoses were made by review of all pertinent medical records according to DSM-IV criteria. Both the patients with schizophrenia and their unaffected siblings performed significantly worse than the nonpsychiatric controls (but did not differ from each other) on verbal and nonverbal cognitive tests at 4 and 7 years of age. Preschizophrenia cases and their siblings were increasingly overrepresented across decreasing quartiles of the performance distributions. There was not significant intra-individual decline, and there were no significant relationships between obstetric complications and test performance among the preschizophrenia subjects. These results suggest that during the period from age 4 to age 7 years, premorbid cognitive dysfunction in schizophrenia represents a relatively stable indicator of vulnerability deriving from primarily genetic (and/or shared environmental) etiologic influences.

Adult↗
PubMed2000

A prospective cohort study of childhood behavioral deviance and language abnormalities as predictors of adult schizophrenia.

Language and behavioral deviance in early childhood in preschizophrenia individuals suggests that the pathologic processes predisposing to schizophrenia are present from early in life. However, the etiologic antecedents of such impairments, and the degree to which they predict adult schizophrenia, have not been conclusively demonstrated. To address this, we examined language and behavioral predictors of adult psychiatric outcome in a population cohort (72 individuals with schizophrenia or schizoaffective disorder, 63 of their unaffected siblings, and 7,941 with no diagnosis) evaluated prospectively with behavioral examinations and a speech and language evaluation at 8 months, 4 years, and 7 years of age. Psychiatric outcome was ascertained via adult treatment contacts, and diagnoses were made by chart review according to DSM-IV criteria. Social maladjustment at age 7 was found to predict adult schizophrenia, and focal deviant behaviors (e.g., echolalia, meaningless laughter) at ages 4 and 7 were significantly associated with both schizophrenia and sibling status. Unintelligible speech at age 7 was a highly significant predictor of adult schizophrenia (odds ratio = 12.7), and poor expressive language ability predicted both schizophrenia and unaffected sibling outcome. Early behavioral and language dysfunction did not differentially characterize preschizophrenia subjects with a history of fetal hypoxia or an early age of first treatment contact. Given that unaffected siblings show similar signs of deviance, such problems may indicate genotypic susceptibility to the disorder, or shared environmental influences, or both.

Adult↗
PubMed2000

Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort.

OBJECTIVE: Although case-control investigations have shown an association between obstetric complications and schizophrenia, particularly among patients with early onsets, cohort studies have mostly failed to confirm this effect. The authors examined whether a history of fetal hypoxia and other obstetric complications elevated risk for early-onset schizophrenia in a 1955 Helsinki birth cohort. METHOD: The subjects were 80 randomly selected patients with schizophrenia (36 with early and 44 with later onsets) representative of all available probands in the cohort, 61 of their nonschizophrenic siblings, and 56 demographically matched nonpsychiatric comparison subjects. Psychiatric diagnoses were obtained from structured clinical interviews, and obstetric data were taken from standardized, prospectively ascertained obstetric records. A score for hypoxia-associated obstetric complications was entered into logistic regression models, along with measures of prenatal infection and fetal growth retardation. RESULTS: Hypoxia-associated obstetric complications significantly increased the odds of early-onset schizophrenia but not of later-onset schizophrenia or unaffected sibling status, after prenatal infection and fetal growth retardation were taken into account. CONCLUSIONS: These findings support an association between obstetric complications and increased risk for early-onset schizophrenia. The authors advance a model whereby the neurotoxic effects of fetal hypoxia may lead to an early onset of schizophrenia due to premature cortical synaptic pruning.

Adult↗
PubMed1999

Neurodevelopmental processes in the ontogenesis and epigenesis of psychopathology.

Dramatic gains in knowledge have been made in the fields of neuroscience, human development, and developmental psychopathology during the past quarter of a century. Despite the advances that have been achieved in each discipline separately, considerably less progress has occurred in understanding the relation between neurobiological and behavioral development in normal and atypical populations. Research has increasingly demonstrated that abnormalities that occur early in development may result in the emergence of aberrant neural circuitry that eventuates in relatively enduring forms of psychopathology. Knowledge of normal neurobiological development provides a powerful foundation for understanding the contributions that neurodevelopmental processes make to the etiology and sequelae of psychopathology across the life course. An integrated perspective wherein an appreciation of the complex neural, psychological, and social-contextual processes that cohere to bring about normal and pathological outcomes is necessary in order to advance understanding of the genesis and epigenesis of mental disorders. Such an approach will require a reduction of the schisms that so often separate neurobiological and behavioral research.

Aging↗