TNF-α and its soluble receptors mediate the relationship between prior severe mood episodes and cognitive dysfunction in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is one of the most disabling mental health conditions in the world. Symptoms of cognitive impairment in BD contribute directly to occupational and social deficiencies and are very difficult to treat. Converging evidence suggests that BD patients have increased peripheral markers of inflammation. The hypothesis of neuroprogression in BD postulates that cognitive deficits develop over the course of the illness and are influenced by prior severe mood episodes, leading to wear-and-tear on the brain- however, there exists a paucity of data statistically testing a mediating role of immune molecules in cognitive dysfunction in BD. METHODS: This is a cross-sectional study. We measured serum levels of tumor necrosis factor alpha (TNF-α), and soluble (s) TNF receptors one and two (sTNF-R1 and sTNF-R2) in 219 euthymic BD patients and 52 Healthy Controls (HCs). Structural equation modeling (SEM) was used for the primary purpose of assessing whether TNF markers (measured by the multiple indicators TNF-α, sTNF-R1 and sTNF-R2) mediate the effect or number of prior severe mood episodes (number of prior psychiatric hospitalizations) on cognitive performance. RESULTS: BD and HC groups did not differ on circulating levels of TNF molecules in the present study. However, we found higher sTNF-R1 concentration in 'late-stage' BD illness (>1 prior psychiatric hospitalization) compared to those in early stage illness. In the subsequent SEM, we found that the model fits the data acceptably (Chi-square = 49.2, p = 0.3), and had a 'close fit' (RMSEA = 0.02, PCLOSE = 0.9). Holding covariates constant (age, sex, premorbid IQ, education, and race), we found that the standardized indirect effect was significant, p = 0.015, 90%CI [-0.07, -0.01], indicating that the estimated model was consistent with peripheral TNF markers partially mediating a causal effect of severe mood episodes on executive function. CONCLUSIONS: Our results indicate that circulating levels of TNF molecules partially mediate the relationship between prior severe mood episodes and executive function in BD. These results may implicate TNF variables in the neuroprogressive course of BD and could point to novel interventions for cognition.

Epileptic activity following 10 minute cerebral ischemia in Mongolian gerbils: an electrophysiological study.

The effects of bilateral carotid occlusion (BCO) on electroencephalographic (EEG) activity and hippocampal structural integrity was studied in 25 Mongolian gerbils. During BCO EEG became flat in frontal cortex and hippocampus but bilateral spikes and motor signs were recorded during this period. Following release of clamping EEG gradually recovered within 36 h but interictal activity persisted disappearing on the 6th-7th day. At the end of 7 days a selective necrosis of CA1 hippocampal neurons was observed. The results indicate that 10 min cerebral ischemia induces a transient epileptic activity followed by the CA1 neuronal loss. Mechanisms underlying ischemic damage are complex and probably they involve an altered synaptic transmission.

Epileptic activity following cerebral ischemia in Mongolian gerbils is depressed by CPP, a competitive antagonist of the N-methyl-D-aspartate receptor.

A 10-min bilateral carotid occlusion (BCO) in Mongolian gerbils induces transient generalized epileptic discharges in the hippocampal and cortical regions, which are followed by long lasting interictal spiking activity. An initial peak of this activity occurs within 18-36 h after BCO, then it decreases slowly and completely disappears by the 6th-7th day. On the 7th day, morphological evidence shows a selective loss of CA1 hippocampal neurons. 4-(3-Phosphonopropyl)-2-piperazine-carboxylic acid (CPP), a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor was administered (7 or 15 mg/kg i.p.) immediately after clamping, and again every 12 h for 3 consecutive days. It induced a dose-related depression of epileptic activity, while, on the other hand, at both dosages, it always prevented the loss of CA1 neurons. The results are discussed in view of the different mechanisms mediating cell damage and epileptic activity.

The therapeutic role of naltrexone in negative symptom schizophrenia.

1. Naltrexone (50 mg bid, p.o.) was administered in a double-blind fashion (with placebo control) to chronic schizophrenic patients who maintained their routine neuroleptic and anxiolytic therapy. 2. Both positive and negative symptom patients who received naltrexone improved with regard to symptoms involving deterioration and social withdrawal. No significant amelioration was recorded in subjects assuming placebo relative to the same psychopathological areas. 3. Favourable results were obtained mainly from patients affected by negative symptom schizophrenia. 4. Naltrexone may have acted by direct or indirect neurochemical mechanisms related to negative symptom schizophrenia.

A case of stroke associated with gonadotropin treatment in a young patient.

A case of ischemic stroke in a 40-year-old hypofertile man who was given a gonadotropin therapy for a short time is described. We discuss the possible causal relationship between treatment and cerebrovascular accident. A possible pathogenetic mechanism is also proposed.

Protective effect of clonazepam on ischemic brain damage induced by 10-minute bilateral carotid occlusion in Mongolian gerbils.

A 10-min bilateral carotid occlusion (BCO) in a control group of Mongolian gerbils, induced a transient generalized epileptic activity both in the hippocampal and in the cortical regions, associated with motor manifestations. After recirculation, spiking activity persisted, reaching its maximum peak within 18-36 h and then slowly decreasing till its total disappearance on the 6th-7th day. On the 7th day, histological studies manifested a selective loss of CA1 hippocampal neurons. The treated gerbils (divided in 2 groups according to the dosage used) were administered clonazepam (CZP), a benzodiazepine receptor agonist, immediately after clamping and again every 24 h for the following three days at dosages of 0.05 and 0.1 mg/kg i.p., respectively. The drug inhibited epileptic activity in a dose-dependent manner, while it prevented CA1 neuronal loss at both doses. These results point to a possible derangement of the GABAergic system which probably in turn triggers an exaggerated excitation.

Use of psychiatric inpatient services by heavy users: findings from a national survey in Italy.

PURPOSE: To analyze factors associated with a patient's probability of being a Heavy User (HU) of inpatient psychiatric services and to compare the HU inpatient population with Non-Heavy Users (NHUs). PATIENTS AND METHODS: The survey was conducted among inpatients enrolled in the PROGRES-Acute-project, an Italian nationwide survey of public and private inpatient facilities. Patients with three or more admissions over the last 12 months were considered HUs, and patients who had undergone one or two admissions during the same period made up the NHU group. RESULTS: Four hundred and thirty-five (40.5%) were HUs, and 640 (59.5%) NHUs. HUs were younger, more frequently unmarried, unemployed, receiving a disability-pension, and either homeless or living in a residential facility. HUs were more likely to have experienced conflicts with their partners or family members during the week prior to admission. A logistic regression analysis revealed that age, age at first admission, number of life-time admissions, and having been the victim of violence were the most important predictive factors for the HU phenomenon. CONCLUSION: Our study suggests that specific attention should be given to patients' family context, due to its crucial role in daily informal care and in the triggering of events leading to rehospitalization.

Patterns of admission to acute psychiatric in-patient facilities: a national survey in Italy.

BACKGROUND: A proper understanding of patterns of care represents a crucial step in improving clinical decision making and enhancing service provision. Only a few studies, however, have explored global patterns of psychiatric admissions nationwide, and none have been undertaken in Italy. METHOD: Sociodemographic, clinical and treatment-related information was collected for 1577 patients admitted to 130 public and 36 private in-patient facilities in Italy during an index period in the year 2004. All patients were also rated using the 24-item Brief Psychiatric Rating Scale (BPRS) and the Personal and Social Performance (PSP) rating scales. RESULTS: Non-affective psychoses (36%) were the most common diagnoses and accounted to a large extent for compulsory admissions. Private facilities were more likely to admit patients with organic mental disorders and substance abuse/dependence and less likely to admit patients with non-affective psychoses. Overall, 77.8% of patients had been receiving treatment by a mental health professional in the month prior to admission. In 54% of cases, the admission was solicited by patients' family members. The main factors preceding admission were impairment in work or social functioning, social withdrawal, and conflict with family members. Agitation, delusions and/or hallucinations, and the presence of multiple problems were associated with compulsory admissions, whereas depressive and anxiety symptoms were associated with voluntary admissions. CONCLUSIONS: In a mixed, public-private psychiatric care system, like the Italian one, public and private facilities admit patients with widely different clinical characteristics and needs. Family support represents an important resource for most patients, and interventions specifically addressed to relieving family burden are warranted.

Which factors affect the costs of psychiatric residential care? Findings from the Italian PROGRES study.

UNLABELLED: In the latest years, mental hospitals have gradually been replaced by a community-based network of facilities, including non-hospital residential facilities (RFs). Little information is still available about their costs. Our aims were to estimate the costs of Italian RFs and to evaluate which factors affect the cost of RFs and their patients. METHOD: A representative sample of 265 Italian RFs, hosting 2962 patients, was selected for the study. RFs costs and costs of psychiatric, medical and informal care were estimated. RESULTS: Patients in RFs cost between 7851 and 34 650 US$ per year; to this amount, it should be added from 2032 to 4702 US$ per year for the community psychiatric services (CPS). Significant differences were found by facility type, geographical areas, number of beds and age and diagnosis. About 45% of the variability for RF costs and 19% for CPS costs was explained by the regression models. CONCLUSION: The results can be useful to inform service planning and resource allocation.

The prescription of psychotropic drugs in psychiatric residential facilities: a national survey in Italy.

OBJECTIVE: This paper reports the prescriptions of psychotropic drugs made to 2962 patients living in 265 residential facilities (RFs) in Italy. METHOD: Structured interviews were administered to RF managers and staff to obtain data on patients' sociodemographic and clinical characteristics; information about current drug prescriptions were obtained from clinical records. RESULTS: Polypharmacy was common: on average, each treated patient was taking 2.7 drugs (+/-1.1). The association of one atypical antipsychotic with one benzodiazepine represented the most common prescription profile. The variable most consistently associated with a higher likelihood of receiving polypharmacy was a history of admission to an acute general hospital psychiatric ward in the previous 12 months. Many prescriptions were loosely related to specific diagnoses. CONCLUSION: Psychotropic drug prescription patterns for severe patients living in RFs are characterized by substantial rates of polypharmacy. Specific guidelines may be helpful for long-stay patients living in RFs, who exhibit complex care needs.

Tyrosine hydroxylase, neuropeptide Y, substance P, calcitonin gene-related peptide and vasoactive intestinal peptide in nerves of rat periovarian adipose tissue: an immunohistochemical and ultrastructural investigation.

Rat periovarian adipose tissue contains unilocular adipocytes and some multilocular adipocytes that, following acclimation to cold, become more numerous and give rise to periovarian brown fat areas. We studied the occurrence and distribution of tyrosine hydroxylase, neuropeptide Y, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, methionine enkephalin, neurotensin, galanin, and cholecystokinin 9-20 in the nerves of rat periovarian tissue maintained at 20 degrees C (control rats), acclimated at 4 degrees C (cold acclimated rats) and at 28 degrees C (warm-acclimated rats). In the periovarian tissue of control and warm-acclimated rats, tyrosine hydroxylase-like, neuropeptide Y-like, substance P-like and calcitonin gene-related peptide-like immunoreactive elements (putative nerves) were present in the blood vessels. In the periovarian tissue of cold-acclimated rats, we found: (1) a more widespread vascular distribution of these neuropeptides; (2) tyrosine hydroxylase-like and calcitonin gene-related peptide-like immunoreactive elements among paucilocular and multilocular adipocytes (parenchymal-like nerves); (3) vasoactive intestinal peptide-like immunoreactive elements in some arteries. Investigation by EM showed the presence of heterogeneous non-myelinated axons both associated with capillaries and among paucilocular and multilocular adipocytes (parenchymal fibres) in periovarian brown fat areas. In conclusion, periovarian brown fat contains the same neuropeptides, with the same vascular and parenchymal distribution, already seen in typical depots of brown fat.