Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Recent-onset ecstasy use: Association with deviant behaviors and psychiatric comorbidity.

Background: Despite increases in ecstasy (MDMA) use in the United States, little is known about characteristics linked with recent-onset ecstasy use, especially psychiatric symptoms and deviant behaviors. Aims: To test whether individuals with high levels of other drug use are more likely to be recent-onset ecstasy users; to test whether psychiatric symptoms in adults are associated with recent-onset ecstasy use; to explore the association between recent-onset ecstasy use and concomitant deviant behaviors in adolescents and adults. Methods: Data from the 2001 National Survey on Drug Use and Health. Findings: Recent-onset ecstasy use was significantly more likely to occur among adolescents and adults (18-34 years old) who engaged in deviant behaviors during the past year as compared with those who did not engage in deviant behaviors during the past year. Higher levels of deviancy indicated a higher likelihood of being a recent-onset ecstasy user, and associations were strongest with nonviolent deviant behaviors such as selling illegal drugs and stealing. Associations between deviant behaviors and recent-onset ecstasy use were similar in strength to associations between deviant behaviors and recent-onset cocaine and marijuana use, respectively. Adults who had past-year psychiatric symptoms (both depressive and panic symptoms) were twice as likely to be recent-onset ecstasy users as compared with those without past-year psychiatric symptoms. Greater levels of drug involvement increased the odds of being a recent-onset ecstasy user. Conclusion: Recent-onset ecstasy use seems to be associated with a range of other behavioral problems and may reflect one aspect of a larger problem behavior syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heterogeneity in Youth Symptom Trajectories Following Psychiatric Crisis: Predictors and Placement Outcome.

The authors examined heterogeneity in symptom trajectories among youths following psychiatric crises as well as the psychosocial correlates and placement outcomes associated with identified trajectories. Using semiparametric mixture modeling with 156 youths approved for psychiatric hospitalization, the authors identified 5 trajectories based on symptoms over the 16 months following crisis: high improved, high unimproved, borderline improved, borderline unimproved, and subclinical. Membership in unimproved symptom groups was associated with less suicidality, younger age, more youth hopelessness, and more caregiver empowerment. Improved symptom group membership predicted long-term decreases in days in out-of-home placements. More important, and in contrast with general impressions from the existing literature, findings suggest that a substantive proportion of youths with serious emotional disturbance sustain high levels of symptomatology following intensive mental health services. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ability of the Millon Clinical Multiaxial Inventory--Third Edition to detect malingering.

This study investigated the ability of the Millon Clinical Multiaxial Inventory--Third Edition (MCMI-III) to discriminate students malingering psychopathology (n=106) from bona fide psychiatric inpatients (n=202). Students were randomly assigned to a fake-bad or an honest-responding condition. Analyses investigated the ability of the modifier indices to discriminate fake-bad group participants from the psychiatric inpatients. Scale X raw cutoff score >178 yielded a positive predictive power (PPP) of 0.0, a negative predictive power (NPP) of 63.1, and a hit rate of 63.1%. Optimal cutoff scores were developed. Scale X Base Rate (BR) >84 provided a PPP of 55.6, an NPP of 72.1, and a hit rate of 65.2%. Scale Y BR     

Treatment of aggression for an adult diagnosed with schizophrenia at a public psychiatric hospital.

The effectiveness of a behavioral program to treat chronic aggression in an adult male individual diagnosed with schizophrenia at a public psychiatric hospital was evaluated. A behavioral plan was developed to provide the client with positive social interactions, social skills training, and positive reinforcement for prosocial behavior; no negative consequences were implemented. The number of aggressive acts declined with the introduction of the behavioral plan and ultimately remitted even without ongoing reinforcers. This article demonstrates the value of psychological intervention in treating aggression with a treatment-resistant client in an in-patient setting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Invariance properties of RAMS and linear time

An operation on integers isLTTC if it is computable in linear time on a Turing machine (using the dyadic or binary representation of integers). AnLTTC-RAM (respectivelyI-RAM) is a RAM which only uses LTTC operations (respectively operations in the setI).The address-free time complexity measure of a RAM evaluates execution times using the logarithmic cost criterion but assumes that addressing operations are performed for free.     

Childhood Sexual and Physical Abuse and the 1-Year Prevalence of Medical Problems in the National Comorbidity Survey.

In a population sample (N = 5,877; ages 15 to 54), the authors found childhood sexual and physical abuse to be associated with the 1-year prevalence of serious health problems for both men and women. The authors also found that participants' psychiatric disorders partially mediated the effects of physical and sexual abuse on adult health. However, childhood abuse continued to independently influence health status after the authors controlled for psychiatric disorders. Contrary to expectations, individuals who experienced a combination of sexual and physical abuse did not have a higher frequency of health problems than those who experienced either type of abuse alone. Implications for these findings are discussed, including possible mechanisms that may account for the association between childhood abuse and adult health problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality Organizations, Psychiatric Severity, and Self and Object Representations.

This study examined the hypothesis that psychotic, borderline, and neurotic personality organizations (POs) present a progressive differentiation between self and object representations and an increasing integration of their bad and good aspects. Fifty patients participated in the study. Measures included scales of self and object representations (S. J. Blatt, S. A. Bers, & C. E. Schaffer, 1993; S. J. Blatt, H. Wiseman, E. Prince-Gibson, & C. Gatt, 1991), as well as the Personality Organization Diagnostic Form (L. Diguer & L. Normandin, 1997) and estimations of psychiatric severity. Results showed that PO groups differed in terms of the integration of the object and its valence. It was also observed that although object and self representations were closely intertwined, the latter showed more discrimination between POs than the former. Psychiatric severity was shown to correlate more with object representations than self representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Updates on the Risk of Neuropsychiatric and Gastrointestinal Comorbidities in Rosacea and Its Possible Relationship with the Gut–Brain–Skin Axis

Rosacea is a common chronic cutaneous inflammatory disorder. Recently, patients with rosacea were identified as having a higher risk of developing various comorbidities such as cardiovascular disease, psychiatric disorders, neurologic disorders, and gastrointestinal disorders. However, the risks of some comorbidities in patients with rosacea are somewhat contradictory, depending upon the study design. Moreover, pathomechanisms associated with the comorbidities of patients with rosacea remain poorly elucidated. The purpose of this review was to provide the most up-to-date evidence on the risks of neuropsychiatric and gastrointestinal comorbidities in patients with rosacea. Moreover, the molecular pathomechanisms associated with neuropsychiatric and gastrointestinal comorbidities in patients with rosacea were evaluated based on recent studies. This review was also intended to focus more on the role of the gut–brain–skin axis in the association of neuropsychiatric and gastrointestinal comorbidities in rosacea.     

The Molecular Basis and Pathophysiology of Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.