008) between BLC and the level of education Workers with post-se

008) between BLC and the level of education. Workers with post-secondary education (n=17; 15.1%) had lower BLCs (256.41±137.08;) compared to those(n=11; 9.8%) with middle- school education (473.64±194.25). Independent-samples t test was applied to evaluate the relationship between BLC and clinical manifestations of lead poisoning. As shown in tables 5 and ​and6,6, no association was found between BLCs and signs and symptoms of lead poisoning

among 112 workers Inhibitors,research,lifescience,medical of the car battery plant. In addition, no correlation was found between BLC and systolic (118.99 mmHg±11.95; P=0.473; r=0.112) and diastolic (78.55 mmHg±9.21; P=0.658; r=−0.033) blood pressures. Table 5 Association between blood lead concentration Inhibitors,research,lifescience,medical and symptoms of lead selleck chemical poisoning among 112 workers of a car battery industry Table 6 Association between mean blood lead concentrations and signs of lead poisoning among 112 workers of a car battery industry Urinary lead concentration (ULC) ranged from 15 to 221 µg/L (mean, 83.67 µg/L±49.78). Linear regression analysis revealed that BLC (beta coefficient=0.843; P<0.001; r2=0.711) was significantly correlated with ULC. The regression equation was BLC=(3.005×ULC)+147.53. Additionally, the backward linear Inhibitors,research,lifescience,medical regression analysis showed significant correlation between BLC, MCV, neutrophil count (NC) and FBS (P=0.012; R2=0.134) according to equation BLC=1385–(10.9×MCV)+(4.17×NC)–(2.97×FBS). Similarly ULC, as determined by ULC=197.19–(30.58×HB)+(7.87×HCT)+(1.58×NC)–(0.77×FBS),

was significantly correlated with hemato-biochemical variables (P=0.002; R2=0.207). There was also a significant correlation between Inhibitors,research,lifescience,medical BLC and mean corpuscular hemoglobin (P=0.011; r=−0.280), mean corpuscular hemoglobin concentration (P=0.006; r=−0.304) and FBS (P=0.010; r=−0.258). No associations were found between BLC and other hematological and biochemical variables (table 4). Discussion Clinical Manifestations We found no association between the clinical manifestations

of chronic lead poisoning and workers’ Inhibitors,research,lifescience,medical BLC. Previous studies on workers of a tile battery factory have also provided similar results.13 Since the studied population was young, one Drug_discovery possible explanation is the sufficient renal capacity to excrete and eliminate lead from the body. Secondly, due to economic and social issues and awareness of , the number of Iranian workers taking legal actions against employers is increasing, since workers are becoming aware of the hazardous health effects of lead. Therefore, inconsistency between symptoms of lead poisoning and BLC is probably due to malingering. In this study, the patients with chronic mild-to-moderate lead poisoning were investigated. According to Baker et al, more severe manifestations of lead poisoning, such as gastrointestinal symptoms (abdominal pain and colic), possible encephalopathy and wrist/ankle extensor muscle weakness, are found with acute exposure and high personnel turnover rate.

Still, the brachial plexus involvement is of the lower plexus onl

Still, the brachial plexus involvement is of the lower plexus only and the lymphadenopathy is extensive. This discrepancy and the lack of pain suggest that compression is not the most likely mechanism. Post-infectious demyelination caused by EBV infection analogous to brachial

neuritis needs to be considered. Confounding both of these diagnoses is the lack of pain at any time during the course of her illness. Furthermore, post-infectious brachial plexopathies more typically involve upper parts of the plexus. Other diagnosis that we considered in this patient were: monomelic amyotrophy/Hirayama Inhibitors,research,lifescience,medical disease in which a history of progression for several years prior to stabilization and a lack lymphadenopathy and demyelination on nerve conduction studies are expected; multifocal Inhibitors,research,lifescience,medical motor neuropathy characterized by lack of sensory involvement and positive response to

IVIG; multifocal CIDP characterized by response to IVIG and lack of EB positive lymphadenopathy; and hereditary predisposition to pressure palsies with expected positive family history, conduction blocks at compressive sites, and histories of nerve palsies with spontaneous improvement. Our patient did not have the characteristics Inhibitors,research,lifescience,medical of these disorders but had onset of her neurological disorder 2-3 weeks after a viral infection suggesting a causal relationship and points out the need to include EBV infection with lymphadenopathy in the differential diagnosis of lesions involving the lower trunk of the brachial plexus and presenting with

painless amyotrophy Inhibitors,research,lifescience,medical of the hand.

Charcot-Marie-Tooth type 1X (CMT1X) disease is inherited as an X-linked dominant trait. Female CMT1X patients are usually mildly affected or even asymptomatic carriers of mutations in the GJB1 gene coding for a gap junction protein called connexin-32 (Cx32). In this report, a five-generation CMT1X family is described from which the new mutation in the GJB1 gene Cys179Gly was Inhibitors,research,lifescience,medical identified. The Cys179Gly mutation is located in the highly conservative domain of the Cx32 protein. Previous functional studies performed in the OSI-744 oocyte system have shown that point mutations in the highly conserved Cx32 cysteine residues result in a complete loss of function of the gap junction. However, despite severe biochemical defects, the Cys179Gly BIX 01294 in vitro mutation segregates with a mild CMT1X phenotype. This study further documents a discrepancy between biochemical effects of GJB1 mutations and the CMT1X phenotype. Keywords: CMT1X disease, novel GJB1 gene mutation, Cx32 protein, loss of function mutations Introduction Charcot-Marie-Tooth disease (CMT) is one of the most common hereditary neuromuscular disorders, occurring with a frequency of 1:2500 (1). After CMT1A, the X-linked dominant form of CMT (CMT1X) is the second most common disease caused mutations on the Xq13.

Another frequently used discrimination approach is multivoxel pat

Another frequently used discrimination approach is multivoxel pattern analysis (MVPA), which uses pattern-classification techniques to extract the signal across multiple voxels. Many studies have used MVPA to discriminate cognitive changes successfully. For example, MVPA has been used to predict the time course of recall behavior in a free-recall task (Polyn et al. 2005), and it has also been used to predict second-by-second changes in perceived stimulus dominance during a binocular rivalry task (Haynes and Rees Inhibitors,research,lifescience,medical 2005). The most important obstacle to the

extensive use of the voxel-based discrimination approach is the large number of voxel sets to be scanned. However, if improvements are made in the computational algorithms, the voxel-based approach will be highly promising as a tool for characterizing and understanding of how information is represented and processed in the brain. In many functional connectivity analysis, the term ROI-wise or voxel-wise is occasionally Inhibitors,research,lifescience,medical used in different documents or software (e.g., in Resting-State fMRI Data Analysis Toolkit (REST) provided by Beijing Normal University (http://www.restfmri.net/), one can calculate ROI-wise or voxel-wise functional connectivity Inhibitors,research,lifescience,medical directly), indicating that both ROI-wise analysis and voxel-wise analysis in functional

connectivity are seed-based approaches. The ROI-wise analysis Inhibitors,research,lifescience,medical estimates the brain connectivity by computing correlation between temporal signals from two predefined ROIs, whereas the voxel-wise analysis correlates functional temporal signals of a seed region with those of other brain voxels (Craddock et al. 2011; Valsasina et al. 2011). The selection of ROIs typically requires a priori knowledge about the underlying problem; therefore, both of these approaches are conceptually different from the reversal coarse-grained method proposed Inhibitors,research,lifescience,medical here. In summary, the current study compared coarse-grained analysis with reversal coarse-grained

analysis by analyzing the functional abnormalities of the hate circuit studied previously by us in patients with MDD over a fine spatial scale (Tao et al. 2011). By computing the intensity of each voxel, we were able to precisely localize the changed site of the hate circuit. Furthermore, our results demonstrated that the voxel-wise time series extracted from the reversal coarse-grained Carfilzomib analysis had several advantages: (1) a larger amplitude of fluctuations was detected, which indicates that the BOLD signals are more synchronized; (2) more significant differences were observed in the functional connectivity related to the ROIs between patients and controls; and (3) a better performance was observed in the discrimination tasks. From a global perspective, coarse-grained analysis is an appropriate method to investigate the significantly different ROIs and functional connectivity.

There has been a tremendous explosion of new scientific and techn

There has been a tremendous explosion of new scientific and technological knowledge. More than 1,500 new journal articles and 55 new clinical trials are entered in the National Library of Medicine database every day.4 Less than 1% of published clinical information is likely to be relevant to a particular patient’s care, but that 1% of new knowledge may be lifesaving. Identifying, accessing the required knowledge, and acquiring the necessary skills and care processes defined in that less than 1% of relevant development takes a focused, almost Herculean effort. There is a burgeoning technology, particularly in the field of cardiovascular medicine with its new diagnostic techniques and interventional

Inhibitors,research,lifescience,medical procedures, that requires new knowledge and technical skills. It has grown increasingly difficult, Inhibitors,research,lifescience,medical if not impossible, for any individual to keep abreast of all advances pertinent to his/her specialty. It has also recently been documented that a physician’s clinical skills decline over one’s career.5 This decline may be the result of a number of factors, including age-related cognition, the ability or even desire to learn new science and knowledge, dated care processes and transitions of care, and

even physician burnout. There are other occupations in which it is essential to maintain and continuously update professional competence Inhibitors,research,lifescience,medical as measured by knowledge, technical skills, and performance. In the airline industry, pilots are continually tested on their knowledge and technical skills using written examinations and flight simulators. Certainly, Inhibitors,research,lifescience,medical the public would not tolerate flying in a plane with a pilot who has not demonstrated continuous achievement of knowledge, technical skills, communication skills, and performance benchmarks to react competently to emergency check details situations. A similar or even higher standard should be set for physicians. The role of the physician is to manage a patient’s illness through the application of science and technology, without pretext Inhibitors,research,lifescience,medical of personal gain and in a compassionate manner that accounts

for the specific gender, social, ethnic, and emotional aspects of the patient. Clinical reasoning is required for proper application of science to individualized treatment decisions, based upon the compilation of historical clues, physical examination abnormalities, and laboratory results. Care of the patient also requires an understanding of the cognitive and Apitolisib psychological impact of illness, including individual needs, preferences, and values. Additionally, there is the expectation that the physician consider the impact of treatment decisions on society, taking into account the cost and appropriate utilization of resources.6 Communication with peers, other members of the health care team, patients, and families remains an essential part of being a competent physician.

In the United States, Europe, and Japan, hepatitis C virus (HCV)

In the United States, Europe, and Japan, hepatitis C virus (HCV) infection is the major etiology of liver cirrhosis and HCC. Hepatitis virus B (HBV) infection, however, is the

leading cause of HCC development in most Asian countries other than Japan. In addition to HBV and HCV infection, alcoholic cirrhosis and metabolic disorders can also act as risk factors for HCC [145]. c-Myc is among the most frequently overexpressed genes in human cancers. Overexpression of c-Myc in hepatic cells leads to the development of hepatocellular Inhibitors,research,lifescience,medical carcinoma [146]. However, an attempt has been made by Pan et al. to suppress the expression of c-myc gene and C-Myc protein in the tumor bearing cell. Polyamidoamine dendrimer modified CNTs (dMWCNTs) were fabricated for the efficient delivery of antisense c-myc Inhibitors,research,lifescience,medical oligonucleotide (asODN) into liver cancer cell line HepG2 cells. asODN-dMWCNTs composites were incubated with HepG2 cells and

confirmed to enter into tumor cells within 15min by laser confocal microscopy. These composites inhibited the cell growth in time and dose dependent means and downregulated the expression of the c-myc gene and C-Myc protein. These composites exhibit Inhibitors,research,lifescience,medical maximal transfection efficiencies and inhibition effects on tumor cells when compared to CNT-NH2-asODN and dendrimer (asODN) alone [123]. Meng et al. constructed a highly effective targeted DDS based on chitosan and folic acid modified SWCNTs for controllable

loading/release of anticancer agent doxorubicin (DOX). The obtained DDS not only effectively killed the hepatocellular carcinoma SMMC-7721 cell lines and depressed the growth of liver cancer but also displayed Inhibitors,research,lifescience,medical much less in vivo toxicity than free doxorubicin [129]. 5.6. Lymph Node Metastasis The presence of lymph node invasion is one of the strongest indicators for prognoses of distant metastasis and survival in most cancers. In the multistep process of cancer metastasis development, invasion into a vascular Inhibitors,research,lifescience,medical or a lymphatic system has generally been believed to be a key step of tumor cell dissemination. Once tumor cells acquire abilities of intravasation and survival in an unfavorable vascular environment, they circulate around the whole body parts to form new tumors at the secondary site [147]. Lymph node metastasis is a powerful predictor of recurrence and death in patients with cutaneous melanoma. Metastasis to regional lymph nodes develops during AV-951 the course of the disease in approximately 30% of patients with cutaneous melanoma [148]. Yang et al. compared the in vitro and in vivo potential therapeutic effect of gemcitabine (GEM) loaded magnetic MWCNTs (mMWCNTs) with that of gemcitabine loaded magnetic-carbon particles (mACs). His finding reflects the high antitumor activity in human pancreatic cancer BxPC-3 cells of both the scientific study systems when compared along with free drug.

The aα-adrenoceptor agonist medetomidine, tested on a delayed alt

The aα-adrenoceptor agonist medetomidine, tested on a delayed alternation task, exerted no effect in young rats, a small effect at 7 to 11 months, and significant

improvement in performance at 17 to 18 months of age.20 On the other hand, according to Takefumi et al,21 physostigmine ameliorated the performance of a place navigation task in 22- to 23-month-old rats, but lost its effect in 26- to 27-month-old rats. To conclude this section, the “middle-aged rat” appears to be a useful and convenient model for MCI, but with the caveat that the therapeutic efficacy of very few of the many candidate drugs tested on this model was later confirmed Inhibitors,research,lifescience,medical beyond doubt in clinical trials. Therefore, the model may generate “false-positive” drugs, ie, drugs very active in the animal tests, but with limited or no clinical Inhibitors,research,lifescience,medical efficacy. Rats with cerebrovascular pathology The correlation between hypertension and memory impairment is well known30 and has been repeatedly confirmed.31,32 Moreover, MCI may be present in the initial stages of cerebrovascular diseases.1,33 SHRs are considered a model of human hypertension and cardiovascular disease. In these animals, a learning impairment,

expressed as more days needed to reach criterion and more errors made, can be observed in a radial maze test at 12 months of age, earlier than in normotensive rats of the Inhibitors,research,lifescience,medical same strain34,35 and other strains at the same Inhibitors,research,lifescience,medical age.24 Less efficient learning, demonstrated by longer latencies in finding the hidden platform, with normal swim speed, was observed by comparing SHRs with normotensive Wistar-Kyoto rats.36 The longer time needed for learning34 and remembering36 observed in the SHR model is reminiscent of the slowing in cognitive performance, accompanied by relatively mild impairments of memory, that characterize vascular cognitive impairment Inhibitors,research,lifescience,medical in humans.37 SHRs show hypertensive brain damage including astrogliosis, cytoskeletal breakdown, and hippocampal atrophy at an

early age,38 and subtle cholinergic deficits.35,36 Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors lowers blood pressure and prevents the cognitive impairment.39 However, the cognitive impairment in SHRs can also be improved by Obatoclax datasheet cognition enhancer agents, such as oxiracetam.40 In conclusion, SHRs show mild cognitive deficits and limited neuropathological lesions, including some damage to the cholinergic system. Therefore, they mimic the initial phases of the vascular cognitive impairment, which may stabilize or progress toward vascular dementia with much severer cognitive impairments. Models of this progression to vascular dementia, could include transient cerebral ischemia,41 bilateral middle artery occlusion,42 and global cerebral ischemia,43 which all induce extensive neuropathological changes associated with MG 132 severe cognitive impairment.

Table II Similarities between main features of a depressive epi

Table II. Similarities between main MG132 proteasome features of a depressive episode in man and chronic mild stress-induced anhedonia in rats. Data in animals are a compilation of results found in the following publications: 11, 14, 19-21, 24, and 36-40. MAO, monoamine oxidase; … Theoretical validity The stress procedure used in these studies was able to induce a decrease in sucrose consumption and/or preference, a decrease in the ability to associate pleasurable events with a particular environment,

(place preference), and an increase in the current threshold necessary Inhibitors,research,lifescience,medical to elicit, self-stimulation behavior. These results obtained by different, research groups using different strains of animals strengthen the idea that, a chronic, mild, unpredictable stress regimen induces a decreased sensitivity to pleasure, ie, an anhedonic state. Anhedonia is one of the two core symptoms of depression. Aspect validity In addition to inducing an anhedonic state, the chronic mild stress

regimen triggers Inhibitors,research,lifescience,medical the development, of several other symptoms of depression. Indeed, Inhibitors,research,lifescience,medical it is able to decrease sexual and aggressive behavior,37 inhibit locomotor activity, and induce a phase advance shift in arcadian rhythm,41 elicit, a body weight loss, hypertrophy of the adrenals,26 hypersecretion of corticosterone,38 and sleep abnormalities.24 However, this stress regimen did not. induce particular anxiety symptoms in two animal models of anxiety, the elevated plus-maze and the social interaction tests.37 Therefore, this simulation Inhibitors,research,lifescience,medical elicits behavioral and physiological abnormalities found in depression, and these effects seem to have some specificity for depressive-like behaviors. Predictive validity Trie different types of antidepressant drugs did not. modify reinforced behaviors in control nonstressed

animals. Medications Inhibitors,research,lifescience,medical effective in antagonizing stress-induced anhedonia include representatives of the tricyclics11,19 monoamine reuptake inhibitors such as fluoxetine and maprotiline,27 Anacetrapib inhibitors of monoamine oxidase such as moclobemide and brofaromine,20,28 and atypical antidepressants such as mianserin.21,39 Electroconvulsive shocks24 and lithium40 are also active in this model. The antagonism of stress-induced anhedonia requires 2 to 4 weeks of treatment, similar to the time course of antidepressant drugs in humans. Inefficacious substances include representatives of tranquilizers such as chlordiazepoxide27; antipsychotics such as risperidone (see above), haloperidol, and chlorprothixene; psychostimulants such as amphetamine; and analgesics such as morphine.28 Therefore, this simulation appears as specific and selective in its response to all categories of clinically used antidepressant treatments, and in its lack of response to other nonantidepressant psychotropics.

Assessments of severity of depression can

Assessments of severity of depression can predict placebo response; mild depressive episodes are more likely to respond to placebo (rates as high as 70%) compared with severe depressive

episodes (rates closer to 30%).1,30,31 The chronicity of the presenting episode is associated with a low placebo response rate.1 Depressed patients who are ill for more than a year have lower placebo response rates (usually less than 30%), and those with depressive Inhibitors,research,lifescience,medical episodes of less than 3 months’ duration have placebo response rates closer to 50%.32 Klein proposed that the relationship between placebo response and episode duration www.selleckchem.com/products/CP-690550.html suggests that some of the placebo response may merely represent spontaneous

remission.33 Patient factors Patient demographic and personality attributes do not consistently distinguish placebo responders and nonresponders in antidepressant trials.34 Fairchild and colleagues35 have proposed that the tendency to respond Inhibitors,research,lifescience,medical while receiving placebo should be viewed as normally distributed in the population: a smaller percentage of patients never respond while receiving placebo, another subset consistently do, and the majority of patients respond under specific conditions of disease or treatment. Inhibitors,research,lifescience,medical Biological factors The dexamcthasone suppression test is the only biological variable that has been reported to predict placebo response.1 Patients who suppress Cortisol secretion in response to dexamcthasone are found to be more likely to respond to placebo (approximately 50%) than nonsuppressors (approximately 10%).1 Inhibitors,research,lifescience,medical A recent study used quantitative electroencephalography (QEEG) to examine brain function in 51 depressed subjects receiving either an antidepressant (fluoxetine or venlafaxine) or placebo, and sought to detect differences between

medication and placebo responders.36 The study Inhibitors,research,lifescience,medical assessed both QEEG power and cordance, a new measure that reflects cerebral perfusion and is sensitive to the effect of antidepressant medication. There were no significant pretreatment differences in clinical or QEEG measures among the four outcome groups. Placebo responders, however, showed a significant increase in prefrontal cordance starting early in treatment that was not seen in medication responders Batimastat (who showed decreased cordance) or in medication nonresponders or placebo nonresponders (who showed no significant change). The authors conclude that “effective“ placebo treatment induces changes in brain function that are distinct from those associated with antidepressant medication. If these results are confirmed, cordance may be useful for differentiating between medication and placebo responders.

74 However, whereas the studies above, as a whole, strongly sugge

74 However, whereas the studies above, as a whole, strongly suggest that plasticity changes in glutamatergic synapses are involved both in the pathophysiology of stress-related diseases and in the action of therapeutic drugs, little is known as to the cellular and molecular mechanisms involved. In particular, most of the drugs currently used for therapy of affective disorders are based on monoaminergic mechanisms, although for some of them a direct effect on NMDA receptor has been claimed.67 Knowledge of the mechanisms whereby drugs interfere with the function of the glutamatergic synapse would be of great, help in the design of new drugs

and therapies. Synaptic plasticity: the action of Inhibitors,research,lifescience,medical antidepressants on LTP It has been repeatedly shown that different experimental Inhibitors,research,lifescience,medical stress protocols (both acute and chronic) impair hippocampal synaptic plasticity, measured as amount, of ITP, the main cellular model of synaptic plasticity. Ill ere is ample literature on this topic, and the reader is addressed to the numerous reviews available.18,58,75 However, the prevalent effect, of antidepressants

has also been shown to be a reduction of hippocampal Inhibitors,research,lifescience,medical LTP, after acute76 or chronic administration.79-82 It has been speculated that antidepressants may induce an LTP-like process which saturates hippocampal synaptic plasticity, so that capacity for further synaptic change is reduced83,84; discussed in ref 58). Interestingly, it. has been showed that acute administration of antidepressants (fluoxetine, Inhibitors,research,lifescience,medical imipramine, tianeptine) may reestablish I TP after acute stress. 66,67,85 Recently it was shown that the action of tianeptine (but not of imipramine) could be linked to reversal of stress-induced

down-regulation of MEK/ERK-MAPK signaling cascade Inhibitors,research,lifescience,medical and activation of Ser831-GluRl phosphorylation.86 However, it is difficult to relate the acute effect on LTP to the therapeutic action of chronic antidepressants; it will be interesting to assess how chronic treatments affect stress-induced impairment of LTP. Presynaptic mechanisms: the action of antidepressants Another neuroplasticity -related problem is the effect, of stress and antidepressants on the presynaptic release of glutamate. Many studies have shown that different paradigms of stress, or corticosterone administration, Anacetrapib induce a rapid and transient increase of extracellular glutamate in prefrontal cortex and hippocampus.87-89 However, in all these studies the chemical information outflow of glutamate was measured by in vivo microdialysis, a technique that cannot, distinguish between exocytotically released glutamate and metabolic glutamate.90 For this reason it has been difficult to relate exactly the effect, of stress to exocytotic glutamate release. We have recently approached the problem by measuring the depolarization-evoked release of glutamate from freshly purified synaptic terminals (synaptosomes) in superfusion.

Three other DA systems have also been described49: (i) a periven

Three other DA systems have also been described49: (i) a periventricular system arising from the dorsal motor vagus nuclei, nucleus of the solitary tract, periaqueductal and periventricular gray, and projecting to midbrain structures including tegmentum, tectum, thalamus,

and hypothalamus; (ii) an olfactory bulb system Inhibitors,research,lifescience,medical arising from the periglomerular cells in the olfactory bulb; and (iii) an incertohypothalamic circuit from the zona incerta to the hypothalamus. DA exerts effects at DA receptors, of which several subtypes have been identified, and, Inhibitors,research,lifescience,medical similarly to 5-HT and NE, DA is taken up into the presynaptic terminal via a DA Tenatoprazole? transporter (DAT). Interestingly, DA nerve terminals in the

prefrontal cortex of humans and other primates contain no DAT, and the DA signal is inactivated by uptake into nearby NE nerve terminals by NET For this reason, NE reuptake inhibitors increase DA availability in the Inhibitors,research,lifescience,medical prefrontal cortex. Along with 5-HT and NE, DA is catabolized by MAO. DA is a precursor for NE, but its role in depression has been far less scrutinized. CSF concentrations of the major metabolite of DA-homovanillic acid (HVA) – are decreased in depressed patients,50,51 and urine levels of 3,4-dihydroxyphenylacetic acid (DOPAC; another metabolite of DA) have been shown to be decreased in depressed patients52 and potentially Inhibitors,research,lifescience,medical associated with suicidal behavior.50 There is evidence from both brain imaging Inhibitors,research,lifescience,medical studies of the DAT53 and postmortem studies54 that DA neurons are

reduced in activity in depression. Depression is highly comorbid with Parkinson’s disease, which is characterized by loss of DA Brefeldin_A cells in the substantia nigra and VTA; however, it should be noted that 5-HT and NE systems are also disrupted in Parkinson’s disease.55-57 Monoamine oxidase inhibitors (MAOIs), which have demonstrated efficacy in treating depression, decrease catabolism of all monoamines including DA. Certain medications that primarily affect the DA system, such as psychostimulants and pramipexole, also have antidepressant efficacy,58-60 particularly in bipolar depression. Future directions for monoamine systems research The monoamine deficiency hypothesis of depression has remained dominant for many years.