ABSTRACT
Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9+/-2.0 ng/ml vs.11.9+/-2.3 ng/ml, p<0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3+/-2.3 ng/ml) compared to those with clozapine (10.2+/-2.0 ng/ml, p<0.001) and typical antipsychotics (10.0+/-2.1 ng/ml, p<0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta=-0.37, t=-3.15, p=0.001) and BDNF levels (beta=-0.26, t=-2.51, p=0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7+/-1.9 ng/ml for males vs.10.4+/-2.1 ng/ml for female, p<0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.
Subject(s)
Antipsychotic Agents/therapeutic use , Brain-Derived Neurotrophic Factor/blood , Institutionalization , Schizophrenia/blood , Schizophrenia/drug therapy , Adult , Aged , Analysis of Variance , Antipsychotic Agents/classification , Chronic Disease , Drug Administration Schedule , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Long-Term Care , Male , Middle Aged , Psychiatric Status Rating Scales , Regression Analysis , Severity of Illness IndexABSTRACT
OBJECTIVE: We have previously found that chronic hypoxia inhibited thyrotropin-releasing hormone (TRH) mRNA expression in rat paraventricular nucleus (PVN). This study presented the effects of hypoxia on TRH secretion in rat hypothalamus, and the norepinephrine (NE) involvement in the modulation of TRH secretion during acute hypoxia exposure. SETTING AND DESIGN: Hypoxia was simulated at altitudes of 5 km (10.8% O2) or 7 km (8.2% O2) in a ventilated hypobaric chamber, and control group was set at local altitude of 2.3 km (15.8% O2). The duration of hypoxia exposure was designed acutely and chronically for 0.5, 2, 24 h, 5, 10, and 30 d, respectively. TRH levels were measured by specific radioimmunoassay. RESULTS: The results showed that hypoxia of 5 km or 7 km significantly enhanced TRH levels of the ME and PVN, and reduced serum T3 levels in most hypoxia-exposed groups. Intraventricular injection (icv) of NE (4 nmol/L) induced a decrease in TRH levels in the median eminence (ME) and PVN, and an increased serum T3 levels following hypoxia of 7 km exposure for 2 h, compared with icv saline control, indicating TRH release increased. The stimulating effect of NE on the TRH secretion was abolished by icv antagonist of adrenergic alpha2-receptor, yohimbine (40 nmol/L). CONCLUSIONS: We conclude that acute and chronic hypoxia exposure produces an inhibition of hypothalamic TRH secretion from the ME and PVN. Central adrenergic system may play a stimulating role through alpha2-receptor in the acute hypoxia-modulating TRH release from rat hypothalamus.
Subject(s)
Adrenergic alpha-Agonists/pharmacology , Hypoxia/drug therapy , Hypoxia/physiopathology , Median Eminence/metabolism , Norepinephrine/pharmacology , Paraventricular Hypothalamic Nucleus/metabolism , Thyrotropin-Releasing Hormone/metabolism , Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/pharmacology , Animals , Atmosphere Exposure Chambers , Atmospheric Pressure , Injections, Intraventricular , Male , Median Eminence/drug effects , Paraventricular Hypothalamic Nucleus/drug effects , Radioimmunoassay , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-2/drug effects , Triiodothyronine/metabolism , Yohimbine/administration & dosage , Yohimbine/pharmacologyABSTRACT
AIM: To study the influences of beta-endorphin (beta-EP) on the responses of thyrotropin-releasing hormone (TRH) in median eminence (ME) and paraventricular nucleus (PVN) of hypothalamus to acute hypoxia in conscious rats. METHODS: Brain TRH, serum T3 and T4 were measured by radioimmunoassay. The male Wistar rats were exposed in a simulated hypobaric chamber at 7000 m altitude (8.2 % O2) for 2 h. beta-EP was given by intraventricular injection (icv) before hypoxia. RESULTS: beta-EP (0.1 or 1 micromol/L, icv) elevated TRH levels of ME by 12 % (P <0.05) and 15 % (P < 0.05) in treated groups comparing with saline control group (4.8+/-0.3) microg/g protein, and enhanced TRH of PVN by 24 % (P <0.05) and 44 % (P < 0.01) in treated groups comparing with control group (180+/-21) ng/g protein during hypoxia. Meanwhile, serum T3 and T4 were significantly decreased (P < 0.05 or P < 0.01). Naloxone 10 micromol/L abolished the effects of beta-EP (0.1 micromol/L) on TRH in ME (P <0.01) and PVN (P < 0.01) as well as T3 and T4. Naloxone (10 micromol/L, icv) alone reduced contents of TRH in ME and PVN (P <0.05 or P <0.01), but increased the levels of serum T3 and T4 (P <0.01). CONCLUSION: beta-Endorphin was involved in the modulation of hypothalamic TRH release of rats during hypoxia, through an inhibitory mechanism of TRH release in ME and PVN of hypothalamus.
