Idiopathic catatonic syndrome in a young male with no prior psychiatric history: a case report.

BACKGROUND: Catatonia is a syndrome characterized by severe psychomotor disturbances such as hypomotility, bradykinesia, and unusual movements. The condition has been described in the context of a wide variety of primary disease processes, including psychotic and mood disorders and numerous general medical conditions. In the medical community, catatonia is misunderstood, under-recognized, and under-treated. There continues to be debate about whether catatonia is an independent syndrome or a secondary expression of other conditions. This is a unique case presentation, as there are few reports describing cases of isolated catatonic syndrome in the absence of any other psychiatric or medical condition. CASE PRESENTATION: We present the case of a 20-year-old previously healthy Caucasian male whose initial presentation to psychiatric care was in the form of an acute catatonic syndrome dominated by mutism, blank staring, and poverty of movement. As the nature of the patient's symptoms precluded the collection of a complete psychiatric  and medical history, we employed a broad differential diagnosis including catatonia due to another medical condition, catatonia as a specifier for a number of mental disorders, and catatonia not otherwise specified. CONCLUSIONS: The presentation of an acute onset of psychomotor symptoms in the absence of a history of mental illness warrants extensive workup to rule out medical causes to ensure effective treatment of any underlying illness. Benzodiazepines are the first-line treatment for catatonic symptoms, and electroconvulsive therapy can be used to resolve symptoms in patients who do not respond to medical intervention.

Computational validity: using computation to translate behaviours across species.

We propose a new conceptual framework (computational validity) for translation across species and populations based on the computational similarity between the information processing underlying parallel tasks. Translating between species depends not on the superficial similarity of the tasks presented, but rather on the computational similarity of the strategies and mechanisms that underlie those behaviours. Computational validity goes beyond construct validity by directly addressing questions of information processing. Computational validity interacts with circuit validity as computation depends on circuits, but similar computations could be accomplished by different circuits. Because different individuals may use different computations to accomplish a given task, computational validity suggests that behaviour should be understood through the subject's point of view; thus, behaviour should be characterized on an individual level rather than a task level. Tasks can constrain the computational algorithms available to a subject and the observed subtleties of that behaviour can provide information about the computations used by each individual. Computational validity has especially high relevance for the study of psychiatric disorders, given the new views of psychiatry as identifying and mediating information processing dysfunctions that may show high inter-individual variability, as well as for animal models investigating aspects of human psychiatric disorders. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.

Disparate insults relevant to schizophrenia converge on impaired spike synchrony and weaker synaptic interactions in prefrontal local circuits.

Schizophrenia results from hundreds of known causes, including genetic, environmental, and developmental insults that cooperatively increase risk of developing the disease. In spite of the diversity of causal factors, schizophrenia presents with a core set of symptoms and brain abnormalities (both structural and functional) that particularly impact the prefrontal cortex. This suggests that many different causal factors leading to schizophrenia may cause prefrontal neurons and circuits to fail in fundamentally similar ways. The nature of convergent malfunctions in prefrontal circuits at the cell and synaptic levels leading to schizophrenia are not known. Here, we apply convergence-guided search to identify core pathological changes in the functional properties of prefrontal circuits that lie downstream of mechanistically distinct insults relevant to the disease. We compare the impacts of blocking NMDA receptors in monkeys and deleting a schizophrenia risk gene in mice on activity timing and effective communication in prefrontal local circuits. Although these manipulations operate through distinct molecular pathways and biological mechanisms, we found they produced convergent pathophysiological effects on prefrontal local circuits. Both manipulations reduced the frequency of synchronous (0-lag) spiking between prefrontal neurons and weakened functional interactions between prefrontal neurons at monosynaptic lags as measured by information transfer between the neurons. The two observations may be related, as reduction in synchronous spiking between prefrontal neurons would be expected to weaken synaptic connections between them via spike-timing-dependent synaptic plasticity. These data suggest that the link between spike timing and synaptic connectivity could comprise the functional vulnerability that multiple risk factors exploit to produce disease.

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia.

We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity might be interrelated factors in pathogenesis, supporting an activity-dependent disconnection theory of schizophrenia. In this theory, disruption of NMDAR synaptic function leads to dysregulated timing of action potentials in prefrontal networks, accelerating synaptic disconnection through a spike-timing-dependent mechanism.

Integrating Insults: Using Fault Tree Analysis to Guide Schizophrenia Research across Levels of Analysis.

The grand challenges of schizophrenia research are linking the causes of the disorder to its symptoms and finding ways to overcome those symptoms. We argue that the field will be unable to address these challenges within psychiatry's standard neo-Kraepelinian (DSM) perspective. At the same time the current corrective, based in molecular genetics and cognitive neuroscience, is also likely to flounder due to its neglect for psychiatry's syndromal structure. We suggest adopting a new approach long used in reliability engineering, which also serves as a synthesis of these approaches. This approach, known as fault tree analysis, can be combined with extant neuroscientific data collection and computational modeling efforts to uncover the causal structures underlying the cognitive and affective failures in people with schizophrenia as well as other complex psychiatric phenomena. By making explicit how causes combine from basic faults to downstream failures, this approach makes affordances for: (1) causes that are neither necessary nor sufficient in and of themselves; (2) within-diagnosis heterogeneity; and (3) between diagnosis co-morbidity.