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A growing importance has been placed on the recognition and supervision of non-motor features of Parkinson's disease (PD). Depression has been estimated to affect one in three individuals with PD and can lead to worse health outcomes and decreased quality of life. Anxiety, apathy and anhedonia further complicate PD outcomes. In this double-blind, placebo-controlled trial, participants (individuals with mild to moderate PD; n = 24) were randomly assigned to treatment (800 mg/d docosahexaenoic acid (DHA) and 290 mg/d eicosapentaenoic acid, a precursor to DHA) or placebo (an equicaloric amount of corn oil). Treatment duration was 6 months. Treatment had no statistically significant effect on rate of change on either Unified Parkinson's Disease Rating Scale or Hoehn-Yahr Scale score. However, 75% of DHA-treated patients, reduced Hamilton Rating Scale for Depression total score by at least 50%, compared with only 25% into the placebo group. At the end of the six-month study, DHA integration reduced the depressive symptoms.

Objective We aimed at evaluating the association between appetite and symptoms of depression and anxiety, cognitive dysfunction, fatigue, and comorbidities in patients on hemodialysis (HD). Design A cross-sectional study was conducted. Setting The study was conducted in an outpatient HD service of a tertiary level academic hospital. Patients A total of 90 patients on HD were evaluated for appetite (during the past week, how would you rate your appetite?), symptoms of depression (Beck Depression Inventory [BDI]) and anxiety (Hamilton Anxiety Rating Scale [HARS]), cognitive dysfunction (Mini Mental State Examination [MMSE]), and comorbidities (Charlson Comorbidity Index). Main Outcome Measure Relationship between appetite and symptoms of depression and/or anxiety, cognitive dysfunction, and comorbidities was assessed. Results In 43 patients, the appetite was very good/good (group 1), in 22, it was fair (group 2), and in 25, it was poor/very poor (group 3). Mean and median BDI were significantly higher in group 3 as well as the percentage of patients with BDI ≥16. Mean and median HARS and the percentage of patients with HARS >13 were significantly higher in group 3. MMSE was significantly lower in group 3 as well as the percentage of patients with MMSE ≤23. Multiple linear regression analysis showed a dependence of appetite by age and BDI ( P = .007 and P = .002, respectively). Conclusions Anorexia is associated with older age and symptoms of depression in patients on HD.

Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.

Although the pathophysiology of gambling is unknown, an involvement of midbrain dopaminergic pathway has been hypothesized. In this study, the association between brain-derived neurotrophic factor (BDNF) and pathological gambling was investigated. We measured BDNF serum levels in (1) video players (n = 10); (2) card players (n = 9); (3) mixed players (n = 21; both video and card players) and (4) age-matched controls (n = 18). Mixed players had increased BDNF serum levels as compared to controls and higher South Oaks Gambling Screen score as compared to card or video players. Thus, the data demonstrate that patients affected by severe pathological gambling show enhanced BDNF serum levels.

Studies performed in animals and humans have suggested a functional interaction between opioid and cholinergic systems in the control of growth hormone (GH) secretion. Moreover, the sex-dependent modulation of GH secretion in humans is well established. To investigate the role of sex and food intake in the regulation of the reciprocal influences of opioids and acetylcholine in the modulation of GH secretion, we studied the GH response to pyridostigmine (PYR) alone and during a naloxone (NAL) infusion in a group of normal men and women before a meal (at 1:00 PM) and postprandially. In women, the response of GH to PYR alone before the meal was significantly lower than in the men (area under the curve [AUC], mean +/- SEM, 320.18 +/- 87.16 v 1,031.06 +/- 333.21 micrograms/L/90 min, P < .01). Before the meal, NAL completely abolished the response of GH to PYR in men (AUC, 1,031.06 +/- 333.21 v 16.50 +/- 7.50 micrograms/L/90 min, P < .01), whereas infusion of NAL did not significantly modify the GH response to PYR in women. Consumption of the meal significantly decreased PYR-induced GH release in both women (AUC, 21.75 +/- 12.75 v 320.18 +/- 87.16 micrograms/L/90 min, P < .05) and men (AUC, 45.75 +/- 18.75 v 1,031.06 +/- 333.21 micrograms/L/90 min, P < .01). Conversely, food intake did not change the effects of NAL infusion on the GH response to PYR either in women or in men. We conclude that the sex-dependent opioid modulation of PYR-induced GH secretion is observed before a meal but not in the postprandial state. Food intake may be hypothesized to influence the cholinergic regulation of GH secretion and the sex-dependent opioid modulation of central cholinergic tone.

Previous studies have shown that food ingestion is not capable of inhibiting the GHRH-induced GH release in anorexia nervosa, at variance with what is observed in normal subjects. Moreover, a cholinergic alteration has been hypothesized in this disorder. In a group of 24 anorectic patients in a stabilized phase of the illness, we tested, before and after a standard meal, the GH response to GHRH alone and after pre-treatment with pyridostigmine, an inhibitor of acetylcholinesterase, and, on a different day, with oxiracetam, which stimulates the central cholinergic neurones. The GH response to GHRH was significantly increased by both drugs in a fasting state. The postprandial response was not significantly modified by pyridostigmine nor by oxiracetam. Neither of these compounds was able to enhance the postprandial GH ‘paradoxical’ response to GHRH in anorectic patients. The lack of effect of both drugs postprandially also suggests a suppression of somatostatinergic activity.

Previously, we have shown that in the opposite extremes of nutritional status, obesity and anorexia nervosa (AN), growth hormone (GH) response to growth hormone-releasing hormone (GH-RH) is not inhibited by the ingestion of a normal 800-cal meal consumed at lunch time (1 pm), which is at variance with results in normal subjects. However, in obese patients the postprandial increase in GH response to GH-RH is inhibited by an infusion of naloxone (NAL). In this study we have tested anorectic patients, performing the following tests at 1 pm: GH-RH test (50 μg IV) or, in a different day session, NAL (1.6 mg/h, starting 30 minutes before GH-RH) + GH-RH test (50 μg IV). The tests were performed in the following three different experimental conditions: (1) short-term fasting studies (lasting from breakfast), (2) long-term fasting studies (from midnight of the day before) and (3) postprandial studies (after a standard meal consumed 1 hour before the test). In AN, the GH response to GH-RH was not influenced by NAL infusion at 1 pm, in both short-and long-term fasting studies (short-term fasting: peak values after GH-RH alone, 26.5 ± 6.5 ng/mL, duirng NAL, 28.0 ± 3.3 ng/mL; long-term fasting: peak values after GH-RH alone, 32.2 ± 6.8 ng/mL, during NAL, 30.6 ± 4.0 ng/mL). A partial NAL-inhibitory effect was instead observed in postprandial studies, as evidenced by the calculation of areas under the curve ([AUCs] 1,662.1 ± 90.0 after GH-RH alone v 1,090.5 ± 245.4 ng/mL/h during NAL). These findings indicate that NAL exerts differential effects in AN before and after a meal. Comparison to the results previously obtained in normal and obese subjects seems to suggest a differential opioid modulation of GH response to GH-RH in AN patients versus normal subjects or patients with obesity.

Little is known about the course of the symptoms of depression/anxiety and the factors predictive of such courses in hemodialysis (HD) patients. This study aimed at evaluating the possible changes of Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HARS) over time, and factors associated with such changes in HD patients.We screened 110 patients for study participation. Of these, 30 were excluded because of dialytic vintage6 months, alcohol/substance abuse, inability to answer to the questionnaires, diagnosis of psychotic or neurological disorders or recent stressful life events. Eighty patients were included in the study and BDI, HARS, Charlson Comorbidity Index, SF-36 Vitality Subscale, Mini-Mental State Examination (MMSE), routine laboratory parameters, C-reactive protein (CRP) and interleukin-6 were measured at baseline. The 18-month course of BDI and HARS was measured in patients with baseline BDI ≤14.At baseline, 42 patients had BDI14 and 38 patients ≤14. In patients with BDI ≤14, the BDI decreased/remained stable in 19 and increased in 19. Patients with increased BDI had lower baseline MMSE (22.6 ± 2.6 vs. 25.9 ± 2.7, p=0.004) and higher baseline serum CRP (6.07 ± 4.2 vs. 1.64 ± 1.59, p=0.003). At multivariate analysis the relationship between BDI changes and MMSE and serum CRP was statistically significant. In 25 patients, the HARS decreased/remained stable, while in 13 it increased. Characteristics of the 2 groups of patients did not differ significantly.In a meaningful proportion of HD patients, symptoms of depression worsen over time, and CRP and MMSE are independent predictors of such change.

The alpha-2-adrenoceptor agonist clonidine is able to stimulate GHRH secretion directly or via beta-endorphin and, therefore, induces a GH release in normal subjects. This effect has been shown to be blunted in alcoholism during early abstinence, due to central alterations of adrenergic mechanisms. To evaluate pituitary responsiveness to direct stimulation with GHRH, we have studied the GH and PRL response to GHRH in 10 alcoholics during early abstinence. Our data indicate that the pituitary response to GHRH is intact in abstinent alcoholics, except in obese patients, who displayed a blunted GH response. GHRH did not increase PRL. The dissociation between clonidine and GHRH in GH stimulation could reveal a different neuroendocrine mechanism, in comparison with other psychiatric disorders (anorexia nervosa), in which such a dissociation is accompanied by a PRL response to GHRH.

Coenzyme Q10 in seminal fluid shows a direct correlation with seminal parameters except in patients with varicocele. To evaluate whether surgical treatment of varicocele could revert CoQ10 abnormalities, we have studied CoQ10 distribution in thirty-three VAR patients, before and 6-8 months after varicocelectomy, twenty patients with idiopathic oligozoospermia, eleven with isolated asthenozoospermia and sixteen normal fertile men. CoQ10 was assayed in total seminal fluid, plasma or cell pellet by HPLC. A significantly higher CoQ10 proportion in seminal plasma in VAR vs. controls (mean +/- SEM: 61.68 +/- 2.41 vs. 41.60 +/- 1.99%, respectively) was present; total CoQ10 correlated with sperm motility in controls, but not in VAR; an inverse correlation between cellular CoQ10 and motility was present in VAR, but not in controls. Postoperatively, a partial reversion was observed, since the plasma-to-total CoQ10 ratio decreased, but the correlation between total CoQ10 and motility was not restored. On the contrary, the peculiar correlation between cellular CoQ10 and motility was no more detectable in postoperative VAR patients. A partial postoperative reversal of abnormalities in CoQ10 distribution and correlation with seminal parameters was therefore present. As seminal plasma CoQ10 reflects an interchange between intracellular and extracellular compartments, its different distribution could cause a greater sensitivity to peroxidative damage and a reduced utilization for energetic purpose.

Previously we demonstrated that coenzyme Q10 (CoQ10) is present in human seminal fluid and shows a direct correlation with seminal parameters except in patients with varicocele (VAR). We have now evaluated CoQ10 distribution in VAR, versus control subjects, in order to discover metabolic abnormalities within this condition. We studied 32 patients with VAR (11 with oligoasthenozoospermia, 13 with asthenozoospermia, and 8 with normozoospermia), and, as controls, the following groups of subjects, matched with VAR patients according to seminal parameters: 16 patients with idiopathic oligozoospermia, 11 patients with isolated asthenozoospermia, and 14 normal fertile men. CoQ10 was assayed in total seminal fluid, plasma, or cell pellet by high-performance liquid chromatography (HPLC). We found a significantly higher proportion of CoQ10 in seminal plasma in VAR; cellular CoQ10 showed an inverse correlation with sperm concentration and motility in VAR, at variance with controls. As seminal plasma ubiquinone reflects an interchange between intracellular and extracellular compartments, the different distribution in VAR patients could represent a greater sensitivity to peroxidative damage and could suggest reduced utilization for energy, which in turn could cause a defective motility even in patients with a normal cell count. These data suggest a pathophysiological role of CoQ10 in seminal plasma and a possible molecular defect in VAR.

In a previous paper it was demonstrated that Coenzyme Q10, a lipidic molecule with important antioxidant properties, is present at remarkable levels in human seminal fluid, and shows a direct correlation with seminal parameters (sperm count and motility). In patients with varicocele, on the contrary, correlation with sperm motility was lacking and a higher proportion of Coenzyme Q10 was found in seminal plasma. In the present study, the levels of Coenzyme Q10 in the cell pellet of spermatozoa, obtained after centrifugation of semen, were evaluated. In nonvaricocele subjects it was observed that a higher concentration of Coenzyme Q10 (expressed as ng of the molecule per million of cells) was present in the spermatozoa of oligospermic and asthenospermic patients (sperm count < 20 x 10(6) spermatozoa ml-1, sperm motility < 40%). This relationship was not observed in varicocele subjects, who also showed slightly lower intracellular absolute values of the conenzyme. Since Coenzyme Q10 is an antioxidant molecule involved in the defence of the cell from free radical damage, higher intracellular concentrations may represent a mechanism of protection of the spermatozoa. In varicocele patients, this mechanism could be deficient, leading to higher sensitivity to oxidative damage.

A great number of metabolic and hormonal derangements have been described in traumatized patients. Plasma concentrations of many substrates, enzymes, and metabolites rise and/or fall, and indices of organ and tissue function change without unequivocal overall patterns. Endocrine variations can mediate a lot of these metabolic pathway dysfunctions; in general two different secretory patterns can be seen in anterior pituitary hormones: an increase of adrenocorticotropic hormone (ACTH), prolactin (PRL), and growth hormone (GH) and a decrease of other hormones [thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH)]. Neurohypophysial hormones can be involved depending on the kind of trauma. Catecholamines, insulin, and glucagon levels also change, and are of fundamental importance in the regulation of intermediate metabolism in such patients.

Thyrotropin releasing hormone (TRH) administration is known to induce a greater TSH response in normal subjects than in obese subjects. In obesity even GH and PRL response to various stimuli are blunted, presumably because of an augmented somatostatinergic tone in obese subjects. Further studies have shown that pyridostigmine (Pyr), an acetylcholinesterase inhibitor, is capable of augmenting GH in obesity by means of somatostatin inhibition. In order to evaluate the possible interference of an increased somatostatinergic tone on TSH secretion, we studied the TSH response to a TRH bolus in 5 obese children with or without a pyr pretreatment. Similarly, we tested a group of 10 obese adult subjects, with TRH alone or TRH plus pyr administration, 30 min or 60 min before TRH. All subjects had a body weight of 30-50% greater than I.B.W. Our data show that a pretreatment with pyr, 60 min before TRH administration, significantly augments the TSH response in adult obese subjects but not in children; the modality of pyr administration seems to be crucial to evidenciate such an alteration since the pyr pretreatment is not effective when administered 30 min before TRH. The absence of this pyr effect in obese children induces to hypothesize that somatostatinergic tone is differentially modulated in children vs adult obese subjects.

Previous studies have indicated different abnormalities of PRL secretion in patients with primary empty sella (PES). Since it is known that endogenous opiates and dopamine interact in modulating PRL secretion, we have studied the effect of an opiate receptor blockade (with Naloxone, NAL, 1.6 mg/h as a continuous infusion) on anterior pituitary hormones and on PRL responsiveness to metoclopramide (MCP), in 10 premenopausal normoprolactinemic patients with PES, studied in follicular phase, in order to investigate neurotransmitter abnormalities present in such a syndrome. NAL failed to significantly affect LH and FSH basal levels; on the contrary, slight but significant increases in PRL and GH secretion were observed. NAL partially blunted the PRL responsiveness to the dopaminergic blockade, which was very marked when tested after MCP alone. These data confirm that the modulation of anterior pituitary hormone secretion is different in PES patients, when compared with normal subjects. The infusion of NAL induced a "paradoxical" increase in hormones (PRL and GH) which are normally stimulated by endogenous opiates; but, on the other side, it blocked the marked PRL responsiveness to the dopaminergic blockade, which is characteristic of PES syndrome. This phenomenon seems to indicate that the relationships between dopaminergic and opiatergic neurons could be modified by the neuroanatomic alteration which is present in this complex syndrome.