Analysis of Educational Attainment in a Mexican Psychiatric Patient Population with Bipolar or Psychotic Disorders.

Schizophrenia has been associated with premorbid poor educational performance and low educational attainment (EA). However, some studies have found positive associations between psychotic disorders and excellent scholastic performance. In the present study, we examined the association between EA and several clinical and nonclinical characteristics in psychiatric patients diagnosed with psychotic or bipolar disorders. Data were obtained from the files of 1132 patients who entered a major Mexico City psychiatric hospital during the years 2009-2010 for the treatment of psychotic symptoms and who were subsequently diagnosed with schizophrenia, bipolar, schizoaffective, or another psychotic disorder. Chi-squared tests, t-tests, and Cox regression analysis were applied to explore associations between EA and factors including gender, familial history of mental illness, premorbid personality characteristics, age of symptom onset, diagnosis, civil status, and current employment. Family history of mental illness decreased the hazard of having lower EA (B = -0.137, p = 0.025, ExpB = 0.872, 95% CI = 0.774-0.983), while a schizophrenia diagnosis independently increased it (B = 0.201, p = 0.004, ExpB = 1.223, 95% CI = 1.068-1.401). In male patients (but not in females), family history of mental illness was significantly associated with higher EA, while in female patients, premorbid schizoid-like personality characteristics were associated with lower EA. For both genders, lower EA was associated with having more children and being employed in manual labor, while higher EA was associated with professional employment. Conclusions: Compared with bipolar disorder, a schizophrenia diagnosis is associated with lower EA; however, familial history of mental illness and premorbid schizoid-like characteristics independently favor higher and lower EA in males and females, respectively. Since lower EA is generally associated with a lower economic status, special preventative attention should be given to students at high risk for schizophrenia, particularly those displaying a schizoid-like personality.

Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models.

INTRODUCTION: Pediatric obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) have been associated with respiratory tract infections and alterations in the intestinal microbiome, respectively. Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) refers to the sudden onset of neuropsychiatric symptoms that are triggered by several infectious and non-infectious factors. Studies indicate that inflammation plays an important etiological role in PANS, as well as in ASD associated with gut dysbiosis. AREAS COVERED: The present review provides an overview of clinical studies of PANS and ASD associated with gastrointestinal symptoms, as well as existing strategies for investigating these syndromes in rodent models. The authors highlight similarities between these syndromes that may provide clues to common etiological mechanisms. EXPERT OPINION: Although data from animal models are consistent with an important role for anti-neuronal antibodies in PANS triggered by GAS infection, we lack models for identifying pathophysiological mechanisms of PANS associated with other infectious and noninfectious triggers. The authors propose an animal modeling strategy that incorporates known vulnerability and triggering factors for PANS into the modeling process. This novel strategy should expand our understanding of the pathophysiology of PANS, as well as facilitate the development of new pharmacological treatments for PANS and related syndromes.

Dataset on c-Fos expression within components of corticostriatal thalamocortical circuits during the expression of a compulsive-like behavior in the female rabbit: Brain-behavior relationships.

The dataset describes regional brain c-Fos expression and a component of maternal nest building behavior ("straw carrying") in 5 late term pregnant rabbits that had been allowed to interact with straw (a nest building material) for a discrete period (30 min), during which repetitive straw carrying behavior was initiated. Animals were sacrificed for brain c-Fos immunoreactivity 1 h after straw was placed into their cage. Regional brain c-Fos expression: Neuronal c-Fos expression is known to associate with a sustained increase in neuronal excitation above resting levels, primarily due to its induction in response to increased glutamatergic input and corresponding activation of the NMDA receptor. In practice, c-Fos expression is taken to be an indication of an increase in "neuronal activity". Importantly, there is a lag of approximately 20 to 30 min between the onset of the stimulus that caused increased excitation, and the initiation of neuronal c-Fos expression, and c-Fos has a cellular half-life of approximately 1 h. Thus, the pattern of brain c-Fos expression within a brain histological section represents a composite snapshot of "superimposed" regional activations that occurred within approximately 30 min to 2 h prior to sacrifice. Behavioral variables: Behavioral variables included in the present dataset are those that reflect the repetitive nature of straw carrying (straw carrying cycle frequency), as well as individual subcomponents of this behavior (collecting straw, interacting with the nest site), and indicators of the "rigidity" of expression of these subcomponents across all cycle repetitions (standard deviations of time spent collecting straw, time spent interacting with nest site). Exploratory Factor Analysis (EFA) with cluster rotation was applied in an exploratory manner in order to clarify correlational relationships between regional c-Fos expression and specific behavioral variables.

Activation of cortical and striatal regions during the expression of a naturalistic compulsive-like behavior in the rabbit.

Nest building behavior in the pregnant rabbit (Oryctolagus cuniculus) can serve as a model for compulsions in obsessive compulsive disorder (OCD). Previous work showed that the "straw carrying" phase of nest building (during which the rabbit repeatedly collects straw in its mouth, carries it into the nest box and deposits it there, and then returns to collect more) is associated with increased c-FOS expression (a marker of neuronal activity) in the orbitofrontal, anterior cingulate, and piriform cortices. In the present study, we quantified c-FOS expression in the caudate and putamen, as well as in the primary motor, somatosensory, and prefrontal cortices of: (1) pregnant rabbits given straw (PREG + STRAW); pregnant rabbits not given straw (PREG); (3) estrous rabbits given straw (ESTROUS + STRAW); and (4) estrous rabbits not given straw (ESTROUS). We found that straw carrying was associated with increased c-FOS expression in the dorsal putamen, ventral caudate, primary motor cortex, and somatosensory cortex. Additionally, a correlational analysis of PREG + STRAW animals revealed that these regions, along with the premotor and prelimbic cortices, were significantly intercorrelated with respect to c-FOS expression, suggesting their "coactivation" during repetitive straw carrying. By contrast, behavioral interactions of non-pregnant (ESTROUS) rabbits with straw (e.g., sniffing, nibbling it) were associated with a distinct pattern of c-FOS expression that included the medial and ventral putamen. c-FOS expression in PREG + STRAW rabbits is similar to patterns of regional brain activity in OCD patients exposed to obsession-provoking stimuli, as well as to those observed in healthy human mothers responding to infant-associated stimuli.

Lost in translation? A critical look at the role that animal models of obsessive compulsive disorder play in current drug discovery strategies.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric illness estimated to affect between 1-3% of the population. In today's literature, there are a number well-validated and convincing animal models of OCD described. Areas covered: Herein, the authors look at the role that animal models of OCD (including transgenic models, deer mouse stereotypy, quinpirole sensitization, post-training signal attenuation, and mouse marble burying) have played in determining the current directions of OCD drug discovery. Specifically, the article reviews new OCD drug therapies currently under investigation including drugs that target glutamate, dopamine, serotonin, and endocannabinoid systems. The authors review the published results of these clinical trials, and critically examine the contribution of animal models to the development of these novel therapies. Expert opinion: Nitric oxide inhibitors, oxycarbazepine, and modulators of serotonin and metabotropic glutamate receptors should be further explored in animal models as well as in clinical trials. Pregabalin, topiramate, lamotrigine, sarcosine, minocycline, L-carnosine, celecoxib, and ondansetron, which have shown promise in clinical trials, should be explored in animal models with the goal of understanding the neurobiology of their effects. A multidisciplinary, interactive approach to OCD drug discovery, where animal models generate neurobiological hypotheses that can be tested in the clinic, and vice versa, should be cultivated.

Activation of the orbitofrontal and anterior cingulate cortices during the expression of a naturalistic compulsive-like behavior in the rabbit.

We propose that maternal nest building in the female laboratory rabbit is a useful model for compulsions in obsessive-compulsive disorder (OCD). This repetitive behavior comprises collecting straw, depositing it into the nest box, and then returning to collect more straw. We reasoned that if "straw carrying" behavior is homologous to compulsive behavior, then it should be associated with activation of prefrontal regions associated with OCD, namely, the orbitofrontal and anterior cingulate cortices (OFC and ACC, respectively). In the present study, we quantified c-FOS immunoreactivity in the ACC, OFC, premotor (PM), infralimbic (IL), prelimbic (PL), and piriform (PI) cortices of: (1) pregnant female rabbits that were given straw (PREG+STRAW); (2) pregnant rabbits that were not given straw (PREG); (3) estrous rabbits that were given straw (ESTROUS+STRAW); (4) estrous rabbits that were not given straw (ESTROUS). After 1h, all females were sacrificed and processed for brain c-FOS immunoreactivity. We found that pregnant rabbits showed lower latencies to interact with the straw than estrous rabbits, and that pregnant rabbits displayed straw carrying, while estrous rabbits did not. c-FOS expression was increased in the OFC, ACC, and PI in the PREG+STRAW compared to all other groups. By contrast, c-FOS expression in all other regions was greater in PREG+STRAW compared to PREG, but not different from ESTROUS+STRAW. These results point to an important role for the OFC, ACC, and PI in initiating repetitive straw-carrying behavior, and further support the proposal that this behavior can serve as a model for compulsions in OCD.