Neuropathology markers and pathways associated with molecular targets for antipsychotic drugs in postmortem brain tissues: exploration of drug targets through the Stanley Neuropathology Integrative Database.

The atypical antipsychotics bind multiple receptor targets, including dopamine D₂ receptors (DRD2), 5-HT₂ receptors (HTR2A), α-2 adrenergic receptors (ADRA2A), and muscarinic receptors (CHRM1/4). Deficits in antipsychotic targets, their associated pathways, and the causal relationships between the various targets were explored using the Stanley Neuropathology Consortium Integrative Database (SNCID; http://sncid.stanleyresearch.

Platelet alpha2A-adrenoceptor function in major depression: Gi coupling, effects of imipramine and relationship to treatment outcome.

Studies suggest alpha2A-adrenoceptors (alpha(2A)AR) dysregulation in major depressive disorder (MDD). Platelet alpha(2A)ARs exist in high- and low-conformational states that are regulated by Gi protein. Although alpha(2A)AR coupling to Gi protein plays an important role in signal transduction and is modulated by antidepressants, it has not been previously investigated.

Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome.

Abnormal beta(2)-adrenoceptor density and beta(2)-adrenoceptor-mediated cyclic adenosine monophosphate (cAMP) responses were inconsistently reported in major depressive disorder. Tricyclic antidepressants downregulate beta-adrenoceptor density and decrease coupling to G(s) protein. Abnormal beta-adrenoceptor coupling may exist in major depressive disorder and may relate to treatment response.

Adrenergic receptor function in panic disorder. II. Neutrophil beta 2 receptors: Gs protein coupling, effects of imipramine treatment and relationship to treatment outcome.

Panic attacks are associated with increased autonomic symptoms, suggesting increased beta 2-adrenergic receptor (beta 2AR) function in PD. Tricyclic antidepressants downregulate beta AR function. Previous studies on beta AR function in PD, however, are inconsistent.

Characteristics of norepinephrine and clonidine displacement of [3H]yohimbine binding to platelet alpha2-adrenoreceptors in healthy volunteers.

Clonidine's estimates of platelet alpha2-adrenoreceptor (alpha2AR) density are substantially lower than yohimbine's. This discrepancy could have contributed to inconsistent results from studies on the role of alpha2AR in depression. Furthermore, few studies have investigated the relative distribution of alpha2AR between the high- and low-affinity states or their Gi protein coupling.

Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls.

The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (beta2AR). Increased sympathetic activity in PTSD could therefore be due to increased betaAR function.

Platelet alpha2-adrenergic receptor coupling efficiency to Gi protein in subjects with post-traumatic stress disorder and normal controls.

Low platelet membrane alpha2-adrenergic receptor (alpha2AR) density and low basal and forskolin-stimulated cyclic adenosine monophosphate responses, which have been reported in post-traumatic stress disorder (PTSD), suggest either abnormal alpha2AR coupling to G(i) protein or dysregulation in post-receptor signal transduction mechanisms. alpha2AR density in the high- and low-conformational states, agonist affinity in both states and coupling to G(i) protein were investigated in 23 drug-free combat PTSD patients and 25 normal controls. alpha2AR coupling measures were not different between PTSD patients and controls.

Adrenergic receptor function in panic disorder. I. Platelet alpha 2 receptors: Gi protein coupling, effects of imipramine, and relationship to treatment outcome.

Various studies suggest alpha 2-adrenergic receptor (alpha 2AR) dysregulation in panic disorder (PD). Platelet alpha 2-AR exist in high- and low-conformational states as a function of their coupling to Gi protein. alpha 2AR coupling is important in signal transduction and is modulated by antidepressants.

The combined effects of chronic ethanol/desipramine treatment on beta-adrenoceptor density and coupling efficiency in rat brain.

Both ethanol and desipramine influence beta-adrenoceptor regulation. We reported previously that ethanol partially counteracted desipramine's effects on beta-adrenoceptor. Previous studies utilized beta-adrenoceptor radioligands that also bind to 5-HT1B receptors, thus, changes in 5-HT1B receptors could have confounded the results.

Characteristics of agonist displacement of [3H]ketanserin binding to platelet 5-HT2A receptors: implications for psychiatric research.

Brain 5-HT(2A) receptors exist in two agonist affinity states as a function of their coupling to Gq protein. This has not yet been shown in platelets. We examined [3H]ketanserin's saturable binding to platelet 5-HT2A receptors and characteristics of agonist displacement curves of [3H]ketanserin binding in healthy control subjects.

Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet alpha 2 receptors: Gi protein coupling, phase of menstrual cycle, and prediction of luteal phase symptom severity.

Background: Abnormal alpha 2-adrenergic receptor (AR) function is implicated in anxiety and depressive disorders. Premenstrual dysphoric disorder (PMDD) is characterized by anxiety and depressive symptoms, which may be associated with changes in alpha 2AR function. Previous studies on alpha 2AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent.

The relationship between plasma MHPG and NE: employing regression models in estimating centrally derived MHPG and peripheral NE turnover rate in panic disorder.

Studies investigating the role of the noradrenergic system in the pathophysiology of anxiety have focused on measuring plasma 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels. Fewer studies have examined norepinephrine levels. Basal plasma norepinephrine and free MHPG levels were simultaneously measured in 33 normal controls and 20 panic disorder (PD) patients.

Adrenergic receptors in premenstrual dysphoric disorder. II. Neutrophil beta2-adrenergic receptors: Gs protein coupling, phase of menstrual cycle and prediction of luteal phase symptom severity.

Abnormal beta2-adrenergic receptor coupling to Gs protein is implicated in depressive disorders. Steroid hormones and antidepressants modulate beta-adrenergic receptor coupling, which may relate to the therapeutic efficacy of antidepressants. We examined beta2-adrenergic receptors in 18 patients with premenstrual dysphoric disorder (PMDD), in 15 control subjects during the follicular phase and in 12 patients during late luteal phase.

Effects of serotonin and metergoline on 125[I]-iodocyanopindolol binding parameters to beta-adrenergic receptors in rat brain.

Most ligands which have been employed to investigate the regulation of beta-adrenergic receptors (betaAR) under pathophysiological conditions and in response to pharmacological manipulations have also been shown to have affinity for 5-HT1B receptors. We examined the effects of serotonin and metergoline (10 microM) on 125I-iodocyanopindolol (ICYP, 5-100 pM) binding to betaAR in rat frontal cortex and hippocampus membranes. In both brain regions, the presence of either serotonin or metergoline significantly lowered iodocyanopindolol dissociation constant (Kd) and maximum binding capacity (Bmax).

Behavioral, sympathetic and adrenocortical responses to yohimbine in panic disorder patients and normal controls.

Yohimbine, an alpha 2 adrenoreceptor antagonist, enhances norepinephrine (NE) release and increases sympathetic activity. We examined the behavioral, peripheral sympathetic and adrenocortical responses to oral yohimbine in seven healthy controls and 11 patients diagnosed with agoraphobia with panic attacks (PD). Patients did not differ in baseline cardiovascular or neuroendocrine measures from controls despite significantly higher baseline anxiety ratings.

Beta-adrenoreceptor coupling to GS protein in alcohol dependence, panic disorder, and patients with both conditions.

Ethanol may downregulate G-protein-coupled beta-adrenoreceptors (beta AR). beta AR may also be dysregulated in panic disorder (PD). In clinical samples, many patients have comorbid alcohol dependence (AD) and PD.

Indices of brain beta-adrenergic receptor signal transduction in the learned helplessness animal model of depression.

Both stress response and antidepressant drug action may be mediated by beta-adrenergic receptors (beta AR). Since learned helplessness is a stress-induced animal model of depression, beta AR are relevant to investigate in this model. To date, studies have measured changes in total receptor density (RT), but have not examined more detailed aspects of signal transduction mechanisms such as coupling of the receptor to GS protein.

Valproate as an antidepressant in major depressive disorder.

Thirty-three outpatients who met DSM-IV criteria for major depressive disorder (MDD) with no history of manic or hypomanic symptomatology were enrolled in an 8-week open trial of valproate. By Week 4, 15 of the 28 completers (54%) demonstrated a significant clinical response as defined by a score reduction of 50 percent or more or a total score of 9 or lower on the Hamilton Rating Scale for Depression (HRSD). Mean HRSD scores of the completers decreased 48.

Evidence for hypothalamo-growth hormone dysfunction in panic disorder: profile of growth hormone (GH) responses to clonidine, yohimbine, caffeine, glucose, GRF and TRH in panic disorder patients versus healthy volunteers.

Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha 2-adrenergic agonist. However, the mechanism of this blunted response and the role of hypothalamic-GH dysfunction, if any, remains unclear.

Effect of yohimbine on plasma homovanillic acid in panic disorder patients and normal controls.

The effects of oral yohimbine (20 mg) or placebo or both drugs on plasma homovanillic acid (HVA) were evaluated in patients with panic disorder and normal controls. Panic disorder patients had similar HVA values at baseline compared with normal controls, and yohimbine failed to produce appreciable changes in HVA in both groups. These findings are discussed within the context of catecholaminergic theories of panic disorder.

Biogenic amines distribution in the brain of nervous and normal pointer dogs. A genetic animal model of anxiety.

Nervous pointer dogs have been suggested as an animal model for pathological anxiety. In order to study possible disturbances in neurotransmitter functions in this animal model, we measured brain biogenic amines (norepinephrine, dopamine, and serotonin) and their metabolites in both nervous and normal dogs. Eight nervous and six normal dogs were behaviorally tested and later anesthetized and killed.

Multiplicity of depressive episodes: phenomenological and neuroendocrine correlates.

Sixty-four patients with a Research Diagnostic Criteria (RDC) diagnosis of major depressive disorder were categorized into three groups based on their number of depressive episodes (DE): Gr I (1 DE), n = 16, Gr II (2-4 DE), n = 25; and Gr III (5 or more DE), n = 23. All patients were nonsuppressors after 1 mg dexamethasone suppression test (DST) prior to the start of treatment. Patients were monitored during the course of their treatment using serial Hamilton Depression scores and post-DST plasma cortisol levels.