Thought disorder (TD) has long been associated with schizophrenia (SZ) and is now widely recognized as a symptom of mania and other psychotic disorders as well. Previous studies have suggested that the TD found in the clinically unaffected relatives of SZ, schizoaffective and bipolar probands is qualitatively similar to that found in the probands themselves. Here, we examine which quantitative measures of TD optimize the distinction between patients with diagnoses of SZ and bipolar disorder with psychotic features (BP) from nonpsychiatric controls (NC) and from each other. In addition, we investigate whether these same TD measures also distinguish their respective clinically unaffected relatives (RelSZ, RelBP) from controls as well as from each other. We find that deviant verbalizations are significantly associated with SZ and are co-familial in clinically unaffected RelSZ, but are dissociated from, and are not co-familial for, BP disorder. In contrast, combinatory thinking was nonspecifically associated with psychosis, but did not aggregate in either group of relatives. These results provide further support for the usefulness of TD for identifying potential non-penetrant carriers of SZ-risk genes, in turn enhancing the power of genetic analyses. These findings also suggest that further refinement of the TD phenotype may be needed in order to be suitable for use in genetic studies of bipolar disorder.

Several laboratories, including ours, have reported an overrepresentation of craniofacial (CF) anomalies in schizophrenia (SZ). How might this dysmorphology arise in a brain-based disorder? Because the brain and face derive from shared embryologic primordia and morphogenetic forces, maldevelopmental processes may result in both CF and brain dysmorphology.Our approach is 2-pronged. First, we have employed, for the first time in the study of psychiatric disorders, objective measures of CF morphology that utilize an extensive normative database, permitting computation of standardized scores for each subject. Second, we have rendered these findings biologically interpretable by adopting principles of embryology in the analysis of dysmorphology.Dependent measures in this investigation focused on derivatives of specific embryonic primordia and were contrasted among probands with psychotic disorders, their first-degree relatives, and normal controls (NC). Subject groups included patients with a diagnosis of SZ (N = 39) or bipolar (BP) disorder with psychotic features (N = 32), their clinically unaffected relatives (N = 82 and N = 41, respectively), and NC (N = 95) subjects.Anomalies involving derivatives of frontonasal and mandibular embryonic primordia showed a clear association with psychotic illness, as well as familial aggregation in relatives in both diagnostic groups. In contrast, one class of CF anomalies emerged only among SZ probands and their first-degree relatives: dysmorphology arising along the junction of the frontonasal and maxillary prominence derivatives, manifested as marked asymmetries. This class was not overrepresented among the BP patients nor among their relatives, indicating that this dysmorphology appears to be specific to SZ and not a generalized feature of psychosis. We discuss these findings in light of embryologic models that relate brain regions to specific CF areas.

The stimuli for smooth pursuit are thought to be target position and target velocity. These two cues, present in many continuously moving targets, play different roles in motion detection — velocity-sensitive and position-sensitive mechanisms are dominant at slow and fast speeds, respectively. Using a random dot pattern, we examined how position and velocity cues affect smooth pursuit to slow and fast motion. For this target, use of short dot lifetime minimizes position cues (i.e. the individual dots are too ephemeral to be tracked continuously) and maintains velocity cues by spatial integration. Here, we used a random dot pattern moving at slow (4í/s) or fast (16í/s) speeds. At each speed, dot lifetime was set to 45 msec or 1500 msec so that the target contained mainly velocity cues or both velocity and position cues, respectively. Observers tracked the random dot patterns moving either to the left or to the right (randomized from trial to trial, 100% coherence). Smooth pursuit to the fast motion was normal regardless of dot lifetime. For slow motion, however, smooth pursuit was well initiated and maintained only under the long, but not under the short, dot lifetime condition. The results indicate that smooth pursuit eye movements rely primarily on position cues for slow motion and velocity cues for fast motion.

Visual motion perception is normally mediated by neural processing in the posterior cortex. Focal damage to the middle temporal area (MT), a posterior extrastriate region, induces motion perception impairment. It is unclear, however, how more broadly distributed cortical dysfunction affects this visual behavior and its neural substrates. Schizophrenia manifests itself in a variety of behavioral and perceptual abnormalities that have proved difficult to understand through a dysfunction of any single brain system. One of these perceptual abnormalities involves impaired motion perception. Motion processing provides an opportunity to clarify the roles of multiple cortical networks in both healthy and schizophrenic brains. Using fMRI, we measured cortical activation while participants performed two visual motion tasks (direction discrimination and speed discrimination) and one nonmotion task (contrast discrimination). Normal controls showed robust cortical activation (BOLD signal changes) in MT during the direction and speed discrimination tasks, documenting primary processing of sensory input in this posterior region. In patients with schizophrenia, cortical activation was significantly reduced in MT and significantly increased in the inferior convexity of the prefrontal cortex, an area that is normally involved in higher level cognitive processing. This shift in cortical responses from posterior to prefrontal regions suggests that motion perception in schizophrenia is associated with both deficient sensory processing and compensatory cognitive processing. Furthermore, this result provides evidence that in the context of broadly distributed cortical dysfunction, the usual functional specificity of the cortex becomes modified, even across the domains of sensory and cognitive processing.

Background: Since Kraepelin's early distinction between bipolar disorder and schizophrenia, it has been assumed that these disorders represent two different pathophysiological processes, although they share many clinical symptoms. Previous studies showed that velocity discrimination, a sensitive psychophysiological measure of the visual motion system, is deficient in schizophrenia. Here we examined whether the motion processing impairment found in schizophrenia also occurs in bipolar disorder.Methods: We compared 16 bipolar patients, 25 schizophrenic patients, and 25 normal controls on a velocity discrimination task. We measured the psychophysical threshold for velocity discrimination and contrast detection (as a control task) in all subjects.Results: Bipolar patients showed normal velocity discrimination thresholds at intermediate velocities, the range in which velocity cues dominate velocity discrimination, and at low velocities. Schizophrenic patients, however, showed elevated velocity discrimination thresholds at intermediate and low velocities. At higher velocities, both bipolar and schizophrenic patients showed elevated thresholds. All subjects showed normal contrast detection thresholds.Conclusions: Normal velocity discrimination in the intermediate range of velocity indicates unimpaired motion processing in bipolar disorder. The abnormal velocity discrimination of both schizophrenic and bipolar patients at higher velocities may reflect impaired temporal processing rather than impaired motion processing per se. These results suggest that the pathophysiological processes of bipolar disorder and schizophrenia diverge at the stage of visual motion processing, a sensory component mediated primarily in the extrastriate cortex. (c) 2006 Elsevier B.V. All rights reserved.

Motion perception is impaired in many neuropathological conditions, including schizophrenia. Motion perception also declines in the course of normal aging. In this study, we ask whether aging is an additive factor in the motion-discrimination deficits of schizophrenia patients. We examined motion perception in schizophrenia patients (n=44) and non-psychiatric controls (n=40) whose ages ranged from 18 to 55. The tasks included velocity discrimination and contrast detection. Thresholds for each of the two tasks were determined for each subject using psychophysical methods. Schizophrenia patients showed significantly increased thresholds (degraded performance) for velocity discrimination compared with the controls. Degraded performance in patients was not related to age. In controls, however, velocity discrimination thresholds were significantly increased beginning by age 45. Performance on a contrast-detection task, which does not require precise discrimination of motion signals, was not significantly affected by age in either group. Aging, even in its early stages, degrades motion discrimination in normal adults. Aging, however, does not adversely affect motion-discrimination deficits in schizophrenia patients through age 55. A similar motion-discrimination deficit in schizophrenia patients and aging normal adults suggests that the mechanisms underlying motion processing in schizophrenia and normal aging may be associated.

Many schizophrenia patients show degraded detection of coherent motion. This visual deficit may (1) be a consequence of having a specifically schizophrenic psychosis, (2) be a non-specific effect of suffering from a severe illness (i.e., “generalized deficit”), or (3) reflect properties of the visual motion processing system that play an antecedent, possibly causal role in the pathophysiology of a disposition to schizophrenia. To distinguish among these possibilities, we measured the accuracy of detecting the direction of coherent motion in 29 schizophrenia patients, 20 first-degree relatives of schizophrenia patients, 19 patients with bipolar disorder and 33 normal controls. The task requires the integration of dynamic signals from stochastic random dot patterns in order to discern the direction of their motion. Schizophrenia patients, as a group, showed significantly elevated thresholds for detecting the direction of coherent motion, but relatives of schizophrenia patients and patients with bipolar disorder did not differ from normal controls on this task. The results indicate that visual motion integration, normally mediated in motion-sensitive brain areas such as the Middle Temporal Area, is impaired in patients with a clinically manifest schizophrenic psychosis, but is intact in patients with a non-schizophrenic psychosis (bipolar disorder) and in the relatives of schizophrenia patients. Our findings suggest that deficiencies in integrating motion signals, while specific for schizophrenia, do not seem to be a co-familial trait.

Eye movement dysfunctions have been found in a large number of schizophrenic patients and in about half of their first-degree relatives. The distribution of these traits within the families of schizophrenic patients suggests a model of genetic transmission that fits an autosomal dominant model, which we have called the "genetic latent trait model." The model, with seven parameters, was fitted to a U.S. population and the model was cross-validated on an independent Norwegian sample. Although the model does not invalidate other, more conventional solutions to the puzzle of schizophrenic transmission, such as multifactorial transmission, the latent trait model does more easily permit linkage studies and therefore will allow refutation or support from the use of molecular genetics techniques.

Objective: Using functional MRI, we investigated whether, like healthy subjects, patients with schizophrenia show a relative hemispheric specialization in ventrolateral prefrontal cortex (PFC) for spatial and shape working memory (WM). We hypothesized that reduced specialization in schizophrenia would reflect a failure to adopt optimal domain-specific strategies and would contribute to WM deficits.Methods: Twelve healthy subjects and 16 schizophrenia patients performed spatial and shape WM tasks and a non-WM control task. Direct comparisons of the spatial and shape WM tasks assessed specialization.Results: Despite deficient WM performance, both patients and controls showed a relative hemispheric specialization in ventrolateral PFC for spatial (right) and shape (left) WM and did riot differ in this regard.Conclusions: The finding of intact hemispheric specialization in ventrolateral PFC suggests that patients employ the same domain-specific strategies as healthy subjects during spatial and shape WM. Rather than reflecting a failure to adopt the optimal strategy, we hypothesize that WM deficits in schizophrenia reflect impairments of executive processes that are required for WM performance regardless of domain. These processes are associated with activity in the dorsolateral PFC, a region that has been repeatedly implicated in studies of WM. (c) 2005 Elsevier B.V. All rights reserved.

Transitive inference (TI) describes a fundamental operation of relational (e.g., explicit) memory organization [Eichenbaum, H., Cohen, N.J., 2001. From Conditioning to Conscious Recollection: Memory Systems of the Brain. Oxford Univ. Press]. Here we investigate TI in schizophrenia (SZ), a neurocognitive disorder associated with explicit but not implicit memory dysfunction. SZ patients and healthy controls were trained on a series of learned discriminations that were hierarchically organized (A>B, B>C, C>D, and D>E). They were then tested on each training pair and two novel "inference" pairs: AE, which can be evaluated without consideration of hierarchical relations, and BD, which can only be evaluated by hierarchical relations. SZ patients and controls successfully learned the training pairs and correctly responded to the nonrelational AE pairs. However, SZ patients were less accurate than controls in responding to the relational BD pairs, consistent with the hypothesis that higher-level memory processes associated with relational memory organization are impaired in SZ. The results are discussed with respect to the relational memory model and candidate neuro-cognitive mechanisms of TI.