Publications by authors named "Andras Hajnal"

78 Publications

Differential Response in Ethanol Behaviors of Female Rats Given Various Weight Loss Surgeries.

Alcohol Alcohol 2021 Aug;56(5):599-604

The Pennsylvania State University, College of Medicine, Department of Neural and Behavioral Sciences, 700 HMC Crescent road, Hershey, PA 17033.

Aims: Currently, the only effective treatment for morbid obesity and its comorbidities is weight loss surgery (WLS). Growing evidence suggests that different types of WLS, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have differential effects on alcohol consumption in humans and rats. Thus, we aimed to directly compare the effects of these two surgical procedures, for the first time in female rats, and to determine whether presence or absence of the ghrelin-producing stomach tissue has critical influence on postoperative alcohol intake.

Methods: We performed two experiments using an identical behavioral protocol, a continuous-access two-bottle choice protocol for various concentrations of ethanol (EtOH). In Experiment 1, 23 high fat diet (HFD) obese, female rats were randomized to three groups: RYGB, SG or sham-operated food-restricted (Sham) controls. In Experiment 2, HFD obese female rats received either sham (n = 11) or a modified RYGB surgery where the remnant stomach was removed (RYGB-X; n = 12).

Results: SG rats drank significantly less than RYGB for 4, 6 and 8% and significantly less than Sham for 6, 8 and 8% reinstatement. RYGB-X consumed significantly less EtOH than Sham across all concentrations, reaching significance for 6 and 8% reinstatement.

Conclusion: These findings confirm reduced EtOH consumption by female SG rats as opposed to increased intake following RYGB, and provide the first experimental evidence that the remnant stomach in the RYGB procedure is contributory. Future studies in rats and humans are warranted to confirm that ghrelin plays a critical role in susceptibility to AUD development following WLS.
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http://dx.doi.org/10.1093/alcalc/agab054DOI Listing
August 2021

Minor Physical Anomalies in Bipolar Disorder-A Meta-Analysis.

Front Psychiatry 2021 16;12:598734. Epub 2021 Jun 16.

Department of Psychiatry and Psychotherapy, Medical School, University of Pécs, Pécs, Hungary.

Minor physical anomalies (MPAs) may reflect basic neurobiological features underlying bipolar disorders (BPD), as they are sensitive physical indicators of morphogenetic failure of the brain. Despite several researches about the presence of MPAs in BPD, the results are still controversial. The aim of the present meta-analysis was to assess the standardized weighted mean effect sizes of MPAs in BPD and to examine if MPAs may be found predominantly in the head and/or facial regions in BPD patients compared to controls (HC). Four studies, involving 155 patients with BPD, and 187 HC, were involved in the analysis after searching the literature. For the investigation of MPAs in the peripheral (MPA-P) and in the head and facial regions (MPA-CF), two studies involving 121 BPD patients, and 133 HC passed the inclusion criteria. The number of the MPAs in the BPD group was significantly higher compared to HC. Another important finding of the present study is that BPD patients' MPA-P scores do not significantly differ from those of the HC. In contrast, BPD patients' MPA-CF scores were found to be significantly higher compared to HC subjects. It is important to note that there was a low number of eligible publications included, which caused higher heterogeneity. Low quality of evidence suggests that MPAs are more common in patients with BPD than in HC and the higher rate of MPAs is found predominantly in the head and facial regions.
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http://dx.doi.org/10.3389/fpsyt.2021.598734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242170PMC
June 2021

Changes in the Gut Microbiota Following Bariatric Surgery Are Associated with Increased Alcohol Intake in a Female Rat Model.

Alcohol Alcohol 2021 Aug;56(5):605-613

Institute for Genome Sciences, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA.

Aims: We aimed to investigate if differences in gut microbiota diversity and composition are associated with post-operative alcohol intake following bariatric surgery in a rat model.

Methods: Twenty-four female rats were randomized to three treatment groups: sham surgery, vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). Stool was collected pre- and post-operatively and 16S rRNA gene amplification and sequencing was performed. Analysis focused on correlating microbial diversity, type of surgery and alcohol (EtOH) intake.

Results: Pre-operative stools samples on regular diet showed similar taxonomic composition and Shannon diversity among the three treatment groups. There was a significant decrease in Shannon diversity and a change in taxonomic composition of the gut microbiota after rats was fed high fat diet. Post-operatively, the RYGB group showed significantly lower taxonomic diversity than the VSG and sham groups, while the VSG and sham groups diversity were not significantly different. Taxonomic composition and function prediction based on PICRUSt analysis showed the RYGB group to be distinct from the VSG and sham groups. Shannon diversity was found to be negatively associated with EtOH intake.

Conclusions: Changes in the taxonomic profile of the gut microbiota following bariatric surgery, particularly RYGB, are associated with increased EtOH intake and may contribute to increased alcohol use disorder risk through the gut-brain-microbiome axis.
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http://dx.doi.org/10.1093/alcalc/agab041DOI Listing
August 2021

Increased Prevalence of Minor Physical Anomalies Among the Healthy First-Degree Relatives of Bipolar I Patients - Results With the Méhes Scale.

Front Psychiatry 2021 29;12:672241. Epub 2021 Apr 29.

Department of Psychiatry and Psychotherapy, Medical School, University of Pécs, Pécs, Hungary.

Minor physical anomalies are somatic markers of aberrant neurodevelopment, so the higher prevalence of these signs among the relatives of bipolar I patients can confirm minor physical anomalies as endophenotypes. The aim of the study was to evaluate the prevalence of minor physical anomalies in first-degree healthy relatives of patients with bipolar I disorder compared to normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 first-degree unaffected relatives of patients with the diagnosis of bipolar I disorder and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the ear, head, mouth and trunk regions among the relatives of bipolar I patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that both minor malformations and phenogenetic variants were more common among the relatives of bipolar I patients compared to the control group, while individual analyses showed, that one minor malformation (sole crease) and one phenogenetic variant (high arched palate) were more prevalent in the relative group. This is the first report in literature on the increased prevalence of minor physical anomalies among the first-degree unaffected relatives of bipolar I patients. The study support the concept, that minor physical anomalies can be endophenotypic markers of bipolar I affective disorder.
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http://dx.doi.org/10.3389/fpsyt.2021.672241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118159PMC
April 2021

Two-level tumor board operation-based social intelligence that serves the quality of cancer treatment and the prevention of burnout phenomenon

Orv Hetil 2021 02 28;162(9):344-351. Epub 2021 Feb 28.

1 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Klinikai Központ, Onkoterápiás Intézet, Pécs, Édesanyák útja 17., 7624.

Összefoglaló. Bevezetés és célkitűzések: Az együttműködés, a csoportmunka életünk szinte minden területén képes növelni a hatékonyságot. A rákgyógyításban már évtizedek óta alkalmazott onkoteamek működését vizsgálva, annak egyértelmű célja az orvosi hatékonyság, az egymástól tanulás és a jogi védelem biztosítása. Jelenleg egy másik aspektust hangsúlyozva próbáljuk bemutatni a kooperatív munka működését, megvilágítva a kommunikációban részt vevők lehetőségeit és dilemmáit, illetve legfőképpen a pszichés támogató hatást. Módszer és eredmények: A Pécsi Tudományegyetem Klinikai Központjának Onkoterápiás Intézetében 12 éve működik a kétlépcsős onkoteamrendszer. Az onkoterápiás megbeszéléseken egyéves időszak alatt 21 orvos, több adminisztrátor, klinikai kutatási munkatárs, szakdolgozó, gyógyszerész és pszichológus vett részt, a résztvevők szakmai tapasztalata igen széles spektrumot fedett le. A megbeszélések során az egyes betegek onkológiai életútja került részletes diszkusszióra interaktív formában, végül a döntési részletek rögzítésre kerültek a központi informatikai rendszerben. Megfigyeléseink rávilágítottak a csapatmunka előnyeire, illetve a csoport által ellátott feladatok megosztó, kiegyensúlyozó, oktatást segítő hatásaira. Az orvosok által kitöltött kérdőívek pedig bizonyították, hogy a közvetlen munkatársak közötti szakmai megbeszélés, egyféle "Bálint-csoport" működésként a pszichés terhek megosztásában is szerepet játszhat. Következtetés: A rákgyógyítás területén az elmúlt évek során bekövetkezett gyors fejlődés, a fokozott elvárások, illetve az ezen a területen végzett, sokszor igen összetett és lelkileg is megterhelő szakmai munka kiemelten fontossá teszi a hatékony minőségbiztosítási módszerek és együttműködési formák alkalmazását, melyek segítségével lehetőség nyílik a szakmai eszmecseréken át a többirányú tudástranszferre és a kiégést megelőző csoportventilációra. Orv Hetil. 2021; 162(9): 344-351.

Summary:

Introduction: The teamwork, the cooperation is always able to elevate effectiveness in every field of life. The tumor board meetings which are widely used in cancer treatment process in the last decades were originally established to warrant the medical, educational and legal quality assurance. Over these aspects, here we present the possibilities and dilemmas of the team work in the communication practices and most of all the psychological support of the participants.

Method And Results: The two-level oncotherapy tumor board system was introduced 12 years ago at the Institute of Oncotherapy, Clinical Center, University of Pécs. During a one-year long observation period, 21 physicians and several administrators, study coordinators, pharmacists, nurses and psychologists with different experiences participated in the oncotherapy tumor board discussions. In the meetings, the specific cancer histories of the patients were analyzed in an interactive form, and finally the detailed decisions were stored in the medical database system. Our observations proved the advantages, moreover, the task sharing, balancing and educational effects of the teamwork. The results obtained from the questionnaires filled out by the physicians proved that the direct conversation between department colleagues works like a case-discussing "Bálint-group" in taking the role of distributing of the psychological burden of the physicians.

Conclusion: The immense advancements in cancer treatment during the last years, moreover, the increased expectations and the complex and mentally charging professional tasks all demand the establishment of more effective quality control and cooperation methods. Introducing these new methods, it would lead to more efficient professional discussions, knowledge transfer and burnout preventive group-related psychological ventilation. Orv Hetil. 2021; 162(9): 344-351.
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http://dx.doi.org/10.1556/650.2021.32032DOI Listing
February 2021

Vagotomy increases alcohol intake in female rats in diet dependent manner: Implications for increased alcohol use disorder after roux-en-y gastric bypass surgery.

Physiol Behav 2021 06 4;235:113309. Epub 2021 Jan 4.

The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, United States.

A variety of weight loss surgeries have been developed to fight the obesity epidemic, with Roux-en-Y gastric bypass (RYGB) being one of the most effective and popular procedures. However, the underlying mechanisms behind its efficacy are still not well understood. Furthermore, growing clinical evidence suggests that RYGB may result in increased risk for development of alcohol use disorder (AUD). The vagus nerve is a potentially critical contributor to increased risk of AUD following RYGB due to the potential for significant damage to the vagus during surgery, which has been confirmed in rodent studies. Studies aiming at the mechanisms underlying development of alcohol or substance use disorders following the surgery have exclusively used male rats, despite the majority of RYGB patients being female. Thus, the current study had two objectives: 1) to investigate the effect of RYGB on ethanol (EtOH) intake in female rats using a protocol previously established in male rats, and 2) to test the effect of vagal damage and high fat diet (HFD) on EtOH intake in female rats. In the first study, 22 female rats were maintained on HFD for four weeks and then split into two surgical groups, RYGB (n = 10) and Sham (n = 12). All rats then underwent a two-bottle choice test of increasing EtOH concentrations: 2%, 4%, 6%, 8%. Rats were then forced to abstain from EtOH for two weeks, after which access to 8% EtOH was reinstated. The RYGB female rats significantly increased their intake for low concentrations of EtOH (2% and 4%) and during the reinstatement period for 8%. These results mirror those seen in male rats, and thus, confirms RYGB in female rats as an equally viable model to males. In the second study, 40 female rats were separated into four groups: HFD/Sham, HFD/Vagotomy, normal diet (ND)/Sham, and ND/Vagotomy. All rats then were subjected to the same two-bottle choice test protocol as in the previous study. Rats in the vagotomy condition had significantly greater preference for 2% and 4% EtOH compared with Sham-operated controls. EtOH intake, either in ml or adjusted for body weight, was greater in rats maintained on ND compared with rats maintained on HFD. These data suggest that vagal damage may, at least in part, contribute to increased preference for EtOH. Furthermore, this increase in EtOH preference is counter to the blunting effect of HFD. In conclusion, the data presented here suggest a role for vagal damage in risk of AUD after weight loss surgery.
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http://dx.doi.org/10.1016/j.physbeh.2021.113309DOI Listing
June 2021

Prolonged functional cerebral asymmetry as a consequence of dysfunctional parvocellular paraventricular hypothalamic nucleus signaling: An integrative model for the pathophysiology of bipolar disorder.

Med Hypotheses 2021 Jan 27;146:110433. Epub 2020 Nov 27.

Psychiatry and Behavioral Health, Penn State University College of Medicine, State College, USA.

Approximately 45 million people worldwide are diagnosed with bipolar disorder (BD). While there are many known risk factors and models of the pathologic processes influencing BD, the exact neurologic underpinnings of BD are unknown. We attempt to integrate the existing literature and create a unifying hypothesis regarding the pathophysiology of BD with the hope that a concrete model may potentially facilitate more specific diagnosis, prevention, and treatment of BD in the future. We hypothesize that dysfunctional signaling from the parvocellular neurons of the paraventricular hypothalamic nucleus (PVN) results in the clinical presentation of BD. Functional damage to this nucleus and its signaling pathways may be mediated by myriad factors (e.g. immune dysregulation and auto-immune processes, polygenetic variation, dysfunctional interhemispheric connections, and impaired or overactivated hypothalamic axes) which could help explain the wide variety of clinical presentations along the BD spectrum. The neurons of the PVN regulate ultradian rhythms, which are observed in cyclic variations in healthy individuals, and mediate changes in functional hemispheric lateralization. Theoretically, dysfunctional PVN signaling results in prolonged functional hemispheric dominance. In this model, prolonged right hemispheric dominance leads to depressive symptoms, whereas left hemispheric dominance correlated to the clinical picture of mania. Subsequently, physiologic processes that increase signaling through the PVN (hypothalamic-pituitaryadrenal axis, hypothalamic- pituitary-gonadal axis, and hypothalamic-pituitary-thyroid axis activity, suprachiasmatic nucleus pathways) as well as, neuro-endocrine induced excito-toxicity, auto-immune and inflammatory flairs may induce mood episodes in susceptible individuals. Potentially, ultradian rhythms slowing with age, in combination with changes in hypothalamic axes and maturation of neural circuitry, accounts for BD clinically presenting more frequently in young adulthood than later in life.
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http://dx.doi.org/10.1016/j.mehy.2020.110433DOI Listing
January 2021

[Irony comprehension in first degree relatives of patients with bipolar disorder - a pilot fMRI study].

Psychiatr Hung 2020 ;35(4):540-546

Pecsi Tudomanyegyetem, AOK, Klinikai Idegtudomanyok Doktori Iskola, Pecs, Hungary, E-mail:

No abstract avalilable.
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December 2020

Differential Effects of Maternal High Fat Diet During Pregnancy and Lactation on Taste Preferences in Rats.

Nutrients 2020 Nov 20;12(11). Epub 2020 Nov 20.

Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

Maternal intake of high fat diet (HFD) increases risk for obesity and metabolic disorders in offspring. Developmental programming of taste preference is a potential mechanism by which this occurs. Whether maternal HFD during pregnancy, lactation, or both, imposes greater risks for altered taste preferences in adult offspring remains a question, and in turn, was investigated in the present study. Four groups of offspring were generated based on maternal HFD access: (1) HFD during pregnancy and lactation (HFD); (2) HFD during pregnancy (HFD-pregnancy); (3) HFD during lactation (HFD-lactation); and (4) normal diet (ND) during pregnancy and lactation (ND). Adult offspring 70 days of age underwent sensory and motivational taste preference testing with various concentrations of sucrose and Intralipid solutions using brief-access automated gustometers (Davis-rigs) and 24 h two-bottle choice tests, respectively. To control for post-gestational diet effects, offspring in all experimental groups were weaned on ND, and did not differ in body weight or glucose tolerance at the time of testing. Offspring exposed to maternal HFD showed increased sensory taste responses for 0.3, 0.6, 1.2 M sucrose solutions in HFD and 0.6 M in HFD-pregnancy groups, compared to animals exposed to ND. Similar effects were noted for lower concentrations of Intralipid in HFD (0.05, 0.10%) and HFD-pregnancy (0.05, 0.10, 0.5%) groups. The HFD-lactation group showed an opposite, diminished responsiveness for sucrose at the highest concentrations (0.9, 1.2, 1.5 M), but not for Intralipid, compared to ND animals. Extended-access two-bottle tests did not reveal major difference across the groups. Our study shows that maternal HFD during pregnancy and lactation has markedly different effects on preferences for palatable sweet and fatty solutions in adult offspring and suggests that such developmental programing may primarily affect gustatory mechanisms. Future studies are warranted for determining the impact of taste changes on development of obesity and metabolic disorders in a "real" food environment with food choices available, as well as to identify specific underlying mechanisms.
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http://dx.doi.org/10.3390/nu12113553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699468PMC
November 2020

The first experiences with the palliative tumor board discussions in the University of Pécs

Orv Hetil 2020 08;161(34):1423-1430

Alapellátási Intézet és Palliatív Medicina Tanszék,Pécsi Tudományegyetem, Általános Orvostudományi Kar, Klinikai Központ, Pécs.

Introduction: Palliative, symptomatic and end-of-life care of advanced and metastatic cancer patients is a great challenge for every health care system. With the initiation and establishment of the multidisciplinary palliative tumor board (MPTB), our aims were the timely referral of patients to palliative care, and the avoidance of multiple unnecessary emergency visits and over-diagnostics without further treatment consequences.

Method And Results: The MPTB meetings were held biweekly. The core members of the team were: palliative care consultant, medical oncologist, internal medicine physician, psychologist, psychiatrist, and oncology and palliative medicine nurses. From May 2019 till January 2020, we discussed the medical history of 97 cases of 93 cancer patients with advanced disease states; in one meeting the team usually discussed over 6-10 complex patient histories. In every case we determined the actual form of the necessary palliative care, e.g., outpatient clinic, home care, or institutional referral, and we decided on further possible and realistic oncology treatment regimes. A few months after the introduction of the new MPTB, we detected a decrease of the unnecessary emergency unit referrals considering the patients whose histories were discussed.

Conclusions: Although the initial MPTB discussions had an intense emotional tone, they shortly became thoughtful and operational expert meetings. We believe that the MPTB system fully promotes the early and timely access of advanced cancer patients to appropriate palliative care and facilitates gradual changes in the medical oncologists' approach from the absolute curative determination to a supportive medical attitude. Orv Hetil. 2020; 161(34): 1423-1430.
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http://dx.doi.org/10.1556/650.2020.31803DOI Listing
August 2020

Roux-en-Y gastric bypass increases GABA-A receptor levels in regions of the rat brain involved in object recognition memory and perceptual acuity.

Physiol Behav 2020 10 6;224:113053. Epub 2020 Jul 6.

Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA. Electronic address:

Roux-en-Y gastric bypass surgery (RYGB), one of the most common and successful procedures for combatting obesity, is associated with post-surgery substance use disorder (SUD) and other addictive behaviors in a subset of patients. We investigated the effects of RYGB on GABA-A receptor levels in the rat brain to identify potential mechanisms of this behavior. The GABAergic system is affected in addiction and has been implicated in the pathology of obesity. We assigned male Sprague-Dawley rats to four groups: standard, low fat diet with sham surgery (control), ad libitum HFD with sham surgery (Sham), calorie restricted HFD with sham surgery (Sham-FR), or HFD with RYGB surgery. Surgery was performed after 8 weeks on the control or HFD diet. Rats maintained their respective diets for 9 weeks post-surgery, then were sacrificed for GABA-A receptor autoradiography using the [H] Flunitrazepam ligand. We identified increased GABA-A binding in the perirhinal cortex of ad-libitum HFD fed rats compared to normal diet controls. RYGB surgery increased GABA-A in the ectorhinal cortex compared to normal diet controls, and increased binding in the jaw region of the primary somatosensory cortex compared to food-restricted rats that received sham surgery. Hypothalamus GABA-A was also negatively correlated with body weight in the RYGB group, where GABA signaling may play a role in obesity regulation. These results suggest that HFD and RYGB modulate GABA signaling in regions important for object recognition memory, and that increased GABA-A levels in the jaw's perceptual field cortex arise from the surgery itself, independent of caloric restriction.
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http://dx.doi.org/10.1016/j.physbeh.2020.113053DOI Listing
October 2020

Consumption of a high energy density diet triggers microbiota dysbiosis, hepatic lipidosis, and microglia activation in the nucleus of the solitary tract in rats.

Nutr Diabetes 2020 06 9;10(1):20. Epub 2020 Jun 9.

Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA, 30602, United States.

Introduction: Obesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (HED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a HED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication.

Objetives: The aim of this study was to investigate the effect of long-term (6 months) consumption of HED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the nucleus of the solitary tract, and systemic inflammation.

Methods: Male Sprague-Dawley rats were fed a low energy density (LED) diet for 2 weeks and then switched to a HED diet for 26 weeks. Twenty-four-hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, 1, 4, 8, and 26 weeks after introduction of the HED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were assessed for 16 S rRNA genome sequencing.

Results: HED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after 4 weeks of HED diet. We further observed changes in the serum cytokine profile after 26 weeks of HED feeding.

Conclusions: These data suggest that microbiota dysbiosis is the first response of the organism to HED diets, followed by increased liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers. To our knowledge, this is the first study to present longitudinal and cross-sectional results on effect of long-term consumption of HED diets on all these parameters in a single cohort of animals.
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http://dx.doi.org/10.1038/s41387-020-0119-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283362PMC
June 2020

Roux‑en‑Y gastric bypass surgery triggers rapid DNA fragmentation in vagal afferent neurons in rats.

Acta Neurobiol Exp (Wars) 2019 ;79(4):432-444

Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, USA;

Previous studies have shown that Roux‑en‑Y gastric bypass (RYGB), one of the most effective weight loss treatments for obesity, results in neurodegenerative responses in vagal afferent gut‑brain connection reflected by microglia activation and reduced sensory input to the nucleus tractus solitarius (NTS). However, it is not known whether RYGB‑induced microglia activation is the cause or an effect of the reported neuronal damage. Therefore, the aim of this study was to establish the order of neurodegenerative responses in vagal afferents after RYGB in the nodose ganglia (NG) and NTS in male and female rats. Sprague‑Dawley rats were fed regular chow or an energy‑dense diet for two weeks followed by RYGB or sham surgery. Twenty‑four hours later, animals were sacrificed and NG and NTS were collected. Neuronal cell damage was determined by TUNEL assay. Microglia activation was determined by quantifying the fluorescent staining against the ionizing calcium adapter‑binding molecule 1. Reorganization of vagal afferents was evaluated by fluorescent staining against isolectin 4. Results of the study revealed significantly increased DNA fragmentation in vagal neurons in the NG when observed at 24 h after RYGB. The surgery did not produce rapid changes in the density of vagal afferents and microglia activation in the NTS. These data indicate that decreased density of vagal afferents and increased microglia activation in the NTS likely ensue as a res ult of RYGB‑induced neuronal damage.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033620PMC
June 2020

Taste Responses in the Nucleus of the Solitary Tract of Awake Obese Rats Are Blunted Compared With Those in Lean Rats.

Front Integr Neurosci 2019 30;13:35. Epub 2019 Jul 30.

Department of Psychology, Binghamton University, Binghamton, NY, United States.

Taste perception changes with obesity but the underlying neural changes remain poorly understood. To address this issue, we recorded taste responses from single cells in the nucleus tractus solitarius (NTS, the first synapse in the central gustatory circuit) in awake, diet-induced obese [(DIO; ≥ 8 weeks on a high-energy diet (45%fat, 17% sugar; HED)], and lean rats. Rats were implanted with a bundle of microelectrodes in the NTS and allowed to recover. Water-deprived rats were allowed to freely lick various tastants in an experimental chamber. Taste stimuli included an array of sapid stimuli dissolved in artificial saliva (AS). Each taste trial consisted of five consecutive licks followed by five AS licks presented on a VR5 schedule. Results showed that taste responses ( = 49 for DIO; = 74 for lean rats) in NTS cells in DIO rats were smaller in magnitude, shorter in duration, and longer in latency that those in lean rats. However, there were proportionately more taste-responsive cells in DIO than in lean rats. Lick coherence in DIO rats was significantly lower than in lean rats, both in taste-responsive, and lick-related cells ( = 172 in lean; = 65 in DIO). Analyses of temporal coding showed that taste cells in DIO rats conveyed less information about taste quality than cells in lean rats. Collectively, results suggest that a HED produces blunted, but more prevalent, responses to taste in the NTS, and a weakened association of taste responses with ingestive behavior. These neural adaptations may represent both negative effects and compensatory mechanisms of a HED that may underlie deficits in taste-related behavior associated with obesity.
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http://dx.doi.org/10.3389/fnint.2019.00035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683675PMC
July 2019

Roux-en-Y gastric bypass in rat reduces mu-opioid receptor levels in brain regions associated with stress and energy regulation.

PLoS One 2019 20;14(6):e0218680. Epub 2019 Jun 20.

Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, United States of America.

Roux-en-Y gastric bypass surgery (RYGB) is the most common and effective weight loss procedure for severe obesity. However, a significant increase in addictive behaviors and new-onset substance use disorder (SUD) are sometimes observed post-surgery. The endogenous opioid system is known to play a major role in motivated behavior and reward, as well as the abuse of substances, including alcohol, tobacco, opioids and highly palatable foods. Here, we examined the effects of RYGB on mu-opioid receptor levels in the brain. Male Sprague-Dawley rats were assigned to one of four groups: standard diet with sham surgery (control), ad libitum high-energy high-fat (HF) diet with sham surgery, calorie restricted HF diet with sham surgery (Sham-FR), or HF diet with RYGB surgery. Control and HF groups were fed their respective diets for 8 weeks, with surgery performed on the eighth week. After 9 weeks on their respective diets post-surgery, animals were sacrificed for mu-opioid receptor autoradiography using the [3H] [D-Ala2,N-Me-Phe4-Gly5-ol]- enkephalin (DAMGO) ligand. Rats with RYGB showed reduced DAMGO binding in the central amygdala compared to sham-operated HF diet controls, and in the hypothalamus compared to high-fat fed Sham-FR. Diet alone did not change [3H] DAMGO binding in any region. These findings show that RYGB surgery, independent of diet or caloric restriction, decreases mu opioid signaling in specific regions important for stress and energy regulation. Thus, RYGB surgery may lead to greater stress sensitivity via downregulated mu opioid signaling in the central amygdala, which may contribute to the observed increased risk in some subjects for addictive behavior.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218680PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586324PMC
February 2020

Neuro-hormonal mechanisms underlying changes in reward related behaviors following weight loss surgery: Potential pharmacological targets.

Biochem Pharmacol 2019 06 4;164:106-114. Epub 2019 Apr 4.

Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, United States.

Currently, the only available effective treatment option for obesity and its comorbidities is weight loss surgery (WLS). Long-term maintenance of weight loss after surgery cannot be explained by caloric restriction or malabsorption alone and has been attributed to unexplained changes in eating behavior. Whether these behavioral changes are related to altered taste or reward functions, or both, are subject to debate. In contrast to reduced food cravings and food addiction following WLS, recent clinical studies have revealed that bariatric surgery patients are prone to an increased risk for substance use disorder (SUD), especially alcohol use disorder (AUD). The substitution of drugs for previously stimulating foods, and the emergence of SUD after WLS, supported by preclinical studies, strongly suggest that manipulation of gut-brain signals may bring about changes in the reward system. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms of reward-related behaviors. Specifically, it explores relevant neural and hormonal changes that present post WLS and their effects on dopaminergic reward pathway and highlights targets for potential pharmacological interventions. Special emphasis is given to recent work suggesting that different types of WLS procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have differential effects on alcohol consumption in humans and rats. These differential effects may hold the key not only to understanding increased substance use following WLS but may also help elucidate the contribution of gut-brain signals to regulation of reward, in general.
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http://dx.doi.org/10.1016/j.bcp.2019.04.004DOI Listing
June 2019

Antidepressant-like effects of insulin and IGF-1 are mediated by IGF-1 receptors in the brain.

Brain Res Bull 2018 10 29;143:27-35. Epub 2018 Sep 29.

Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA. Electronic address:

Depression is associated with uncontrolled diabetes, which indicates a lack of insulin effect, yet the role of the insulin receptor in mediating depression is not clearly established because insulin receptors are not required for glucose entry into the brain. However, insulin receptors are important for brain function since insulin receptor knockout mice have depressive-like activity. Depression and cognitive problems are also associated with low insulin-like growth factor-1 (IGF-1) in the elderly. Rodent studies showed chronic IGF-1 administration had antidepressant-like (AD) activity. We asked if insulin in the brain might act through the IGF-1 receptor, as it does in some tissues. We used acute insulin or IGF-1 infusions into the 3rd ventricle (icv) in rats and tested animals in a forced swim test. We found that antidepressive-like behavior is mediated by insulin and IGF-1. Further, administration of the IGF-1 receptor antagonist JB-1 blocked the antidepressive-like activity of the insulin and IGF-1, indicating a strong relationship between insulin, IGF-1 and depression. Insulin acts at least partially through the IGF-1 receptor and is responsive to receptor antagonism. The model offers promise for future studies of the mechanism of depression, and therapy to increase insulin sensitivity and IGF-1 action including exercise and nutrition.
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http://dx.doi.org/10.1016/j.brainresbull.2018.09.017DOI Listing
October 2018

Roux-en-Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels.

Synapse 2018 Jul 10. Epub 2018 Jul 10.

Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, New York.

Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to four groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed. [ H]SCH 23390, [ H]Spiperone, and [ H]WIN35 428 autoradiography was performed to quantify the effects of diet and RYGB surgery on dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter (DAT) binding. Rats on a chronic HF diet became obese with reduced D1R-like binding within the ventrolateral striatum and the nucleus accumbens core, reduced D2R-like binding in all areas of the striatum and nucleus accumbens core and shell, and reduced DAT binding in the dorsomedial striatum. Restricted HF diet rats showed similar reductions in D1R-like and D2-R-like binding as the obese rats, and reduced DAT binding within all areas of the striatum. Both RYGB and restricted HF diet rats showed similar weight reductions, with RYGB rats showing no difference in binding compared to controls. The observed changes in binding between non-treated obese rats and RYGB rats demonstrates that HF dietary effects on the dopamine system were reversed by RYGB.
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http://dx.doi.org/10.1002/syn.22058DOI Listing
July 2018

Taste and odor preferences following Roux-en-Y surgery in humans.

PLoS One 2018 5;13(7):e0199508. Epub 2018 Jul 5.

Department of Psychology, Binghamton University, Binghamton, New York, United States of America.

It is well established that bariatric surgery, the most effective method to achieve long-term weight loss in obese subjects, reverses enhanced preference and intake of sweet/fatty foods. Although taste and odor preference changes following bariatric surgery have been previously described, their time course and relationship to weight loss remains an issue. The aim of this study was to determine the relationship between taste and odor preference changes and successful weight loss following bariatric surgery. A cross-sectional study was performed on 195 human subjects with body mass index (BMI) above 30 (at least class I obesity), who were scheduled to receive (n = 54) or had previously received (n = 141) Roux-en-Y gastric bypass (RYGB). A Self-Assessment Manikin test was used to measure each participant's affective reaction (ranging from pleasure to displeasure) to a variety of food-related and odor-related pictures. Results confirmed earlier reports about changes in sweet/fatty foods preference after surgery and revealed a shift in preference toward less calorie-dense foods. Relatedly, endorsements of "favorite" foods were mostly sweet/fatty foods in subjects awaiting surgery but were shifted toward more healthy choices, particularly vegetables, in subjects post-RYGB surgery. However, food preference ratings trended toward pre-surgical levels as the time since surgery increased. Answers to open-ended questions about why their diet changed post-surgery revealed that changes in cravings, rather than changes in taste per se, were the major factor. Surprisingly, patients rating a coffee taste as more pleasing after surgery had a lower post-surgical BMI. No associations of odors with change in BMI were apparent. Results showed that following bariatric surgery taste preferences are significantly altered and that these changes correlate with lowered BMI. However, these changes fade as time since surgery lengthens. These results may suggest diagnostic criteria to identify people at risk for less than optimal changes in BMI following bariatric surgery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199508PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033408PMC
December 2018

Altered Neural Activity during Irony Comprehension in Unaffected First-Degree Relatives of Schizophrenia Patients-An fMRI Study.

Front Psychol 2017 9;8:2309. Epub 2018 Jan 9.

Department of Psychiatry and Psychotherapy, Medical School, University of Pécs, Pécs, Hungary.

Irony is a type of figurative language in which the literal meaning of the expression is the opposite of what the speaker intends to communicate. Even though schizophrenic patients are known as typically impaired in irony comprehension and in the underlying neural functions, to date no one has explored the neural correlates of figurative language comprehension in first-degree relatives of schizophrenic patients. In the present study, we examined the neural correlates of irony understanding in schizophrenic patients and in unaffected first-degree relatives of patients compared to healthy adults with functional MRI. Our aim was to investigate if possible alterations of the neural circuits supporting irony comprehension in first-degree relatives of patients with schizophrenia would fulfill the familiality criterion of an endophenotype. We examined 12 schizophrenic patients, 12 first-degree relatives of schizophrenia patients and 12 healthy controls with functional MRI while they were performing irony and control tasks. Different phases of irony processing were examined, such as context processing and ironic statement comprehension. Patients had significantly more difficulty understanding irony than controls or relatives. Patients also showed markedly different neural activation pattern compared to controls in both stages of irony processing. Although no significant differences were found in the performance of the irony tasks between the control group and the relative group, during the fMRI analysis, the relatives showed stronger brain activity in the left dorsolateral prefrontal cortex during the context processing phase of irony tasks than the control group. However, the controls demonstrated higher activations in the left dorsomedial prefrontal cortex and in the right inferior frontal gyrus during the ironic statement phase of the irony tasks than the relative group. Our results show that despite good task performance, first-degree relatives of schizophrenia patients had alterations in the neural circuits during irony processing. Thus, we suggest that neural alteration of irony comprehension could be a potential endophenotypic marker of schizophrenia.
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http://dx.doi.org/10.3389/fpsyg.2017.02309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767266PMC
January 2018

Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling.

Brain Res Bull 2018 04 9;138:26-36. Epub 2017 Aug 9.

Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA. Electronic address:

Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most common surgical options for the treatment of obesity and metabolic disorder. Whereas RYGB may result in greater and more durable weight loss, recent clinical and pre-clinical studies in rats have raised concerns that RYGB surgery may increase risk for alcohol use disorder (AUD). In contrast, recent clinical reports suggest a lesser risk for AUD following VSG, although no preclinical studies have been done to confirm that. Therefore, the present study sought to determine the effects of VSG on ethanol intake and preferences in rodent models using protocols similar to those previously used in animal studies for RYGB. Male Sprague Dawley rats and male C57B6 mice were made obese on a high fat diet (60%kcal from fat) and received VSG or no surgery (controls). All animals then were given access to increasing concentrations of ethanol (2%, 4%, 6%, and 8%), presented for few days each. Compared to controls, VSG rats consumed significantly less of 2, 6 and 8% ethanol and showed significantly reduced preferences to 6 and 8% ethanol over water. VSG mice also displayed reduced intake and preference for 6 and 8% ethanol solutions. After a two-week period of forced abstinence, 8% ethanol was reintroduced and the VSG rats and mice continued to exhibit reduced consumption and less preference for ethanol. Regarding the underlying mechanism, we hypothesized that the removal of the ghrelin producing part of the stomach in the VSG surgery is a possible contributor to the observed reduced ethanol preference. To test for functional changes at the ghrelin receptors, the VSG and control rats were given IP injections of acyl-ghrelin (2.5nmol and 5nmol) prior to ethanol access. Neither concentration of ghrelin resulted in a significant increase in 8% ethanol consumption of VSG or control subjects. Next, the rats were given IP injections of the ghrelin receptor antagonist, JMV (2.5mg/kg body weight). This dose induced a significant reduction in 8% ethanol consumption in the VSG group, but no effect on ethanol intake in the controls. While ghrelin injection was uninformative, increased sensitivity to subthreshold doses of the ghrelin receptor antagonist may indicate reduced ghrelin signaling following VSG. Overall, these findings suggest that bariatric patients with increased susceptibility to AUD may benefit from receiving VSG instead of RYGB surgery, and that changes in ghrelin signaling, at least in part, may play a role in the differential AUD risks between the two most commonly performed bariatric surgical procedures.
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http://dx.doi.org/10.1016/j.brainresbull.2017.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537102PMC
April 2018

Energy-dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation.

Acta Neurobiol Exp (Wars) 2017 ;77(1):18-30

University of Georgia, Veterinary Biosciences and Diagnostic Imaging, Athens, GA, USA,

Obesity is associated with consumption of energy-dense diets and development of systemic inflammation. Gut microbiota play a role in energy harvest and inflammation and can influence the change from lean to obese phenotypes. The nucleus of the solitary tract (NTS) is a brain target for gastrointestinal signals modulating satiety and alterations in gut-brain vagal pathway may promote overeating and obesity. Therefore, we tested the hypothesis that high-fat diet‑induced changes in gut microbiota alter vagal gut-brain communication associated with increased body fat accumulation. Sprague-Dawley rats consumed a low energy‑dense rodent diet (LFD; 3.1 kcal/g) or high energy‑dense diet (HFD, 5.24 kcal/g). Minocycline was used to manipulate gut microbiota composition. 16S Sequencing was used to determine microbiota composition. Immunofluorescence against IB4 and Iba1 was used to determine NTS reorganization and microglia activation. Nodose ganglia from LFD rats were isolated and co-cultured with different bacteria strains to determine neurotoxicity. HFD altered gut microbiota with increases in Firmicutes/Bacteriodetes ratio and in pro-inflammatory Proteobacteria proliferation. HFD triggered reorganization of vagal afferents and microglia activation in the NTS, associated with weight gain. Minocycline-treated HFD rats exhibited microbiota profile comparable to LFD animals. Minocycline suppressed HFD‑induced reorganization of vagal afferents and microglia activation in the NTS, and reduced body fat accumulation. Proteobacteria isolated from cecum of HFD rats were toxic to vagal afferent neurons in culture. Our findings show that diet‑induced shift in gut microbiome may disrupt vagal gut‑brain communication resulting in microglia activation and increased body fat accumulation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382806PMC
http://dx.doi.org/10.21307/ane-2017-033DOI Listing
April 2017

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

Physiol Behav 2017 05 27;173:305-317. Epub 2017 Feb 27.

Department of Veterinary Biosciences & Diagnostic Imaging, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, United States. Electronic address:

Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation.
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http://dx.doi.org/10.1016/j.physbeh.2017.02.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428886PMC
May 2017

Minor physical anomalies in bipolar I and bipolar II disorders - Results with the Méhes Scale.

Psychiatry Res 2017 Mar 5;249:120-124. Epub 2017 Jan 5.

Department of Psychiatry and Psychotherapy, University of Pécs, Faculty of Medicine, Rét u.2.H-7623, Pécs, Hungary. Electronic address:

Minor physical anomalies (MPAs) are external markers of abnormal brain development, so the more common appearence of these signs among bipolar I and bipolar II patients can confirm the possibility of a neurodevelopmental deficit in these illnesses. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in patients with bipolar I and - first in literature - with bipolar II disorders compared to matched healthy control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 30 bipolar I and 30 bipolar II patients, while as a comparison 30 matched healthy control subjects were examined. Significant differences were detected between the three groups comparing the total number of minor physical anomalies, minor malformations and phenogenetic variants and in the cases of the ear and the mouth regions. The individual analyses of the 57 minor physical anomalies by simultaneous comparison of the three groups showed, that in the cases of furrowed tongue and high arched palate were significant differences between the three groups. The results can promote the concept, that a neurodevelopmental deficit may play a role in the etiology of both bipolar I and bipolar II disorders.
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http://dx.doi.org/10.1016/j.psychres.2017.01.014DOI Listing
March 2017

The gut in the brain: the effects of bariatric surgery on alcohol consumption.

Addict Biol 2017 Nov 31;22(6):1540-1553. Epub 2016 Aug 31.

Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.

Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long-term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide. Recent clinical studies have revealed a concern for bariatric surgery patients developing an increased risk for alcohol consumption, and for AUD. A better understanding of the relationship between bariatric surgery and potential later development of AUD is important, given the critical need of identifying patients at high risk for AUD. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms. Special emphasis in this review is given to recent work suggesting that, alterations in alcohol metabolism/pharmacokinetics resulting from bariatric surgery are unlikely to be the primary or at least the only explanation for increased alcohol use and development of AUD, as changes in brain reward processing are also likely to play an important role. Additional studies are needed to clarify the potential role and mechanisms of how bariatric surgery may increase alcohol use and lead to AUD development.
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http://dx.doi.org/10.1111/adb.12436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332539PMC
November 2017

[MENTALIZING DEFICIT IN NEUROLOGICAL DISORDERS: A REVIEW ARTICLE].

Ideggyogy Sz 2015 Nov;68(11-12):364-73

Introduction: Mentalization is the ability to attribute mental states (intentions, desires, thoughts, emotions) to others, and hence to predict their behaviour. This ability fundamentally determines our participation in social relationships and adaptation to society. A significant proportion of the disorders of the central nervous system (CNS) affects those brain structures and neurotransmitter systems that play a role in the mentalizing processes. Accordingly, a number of CNS disorders may be associated with mentalizing deficits, which may affect the outcome of these diseases. Here, we review recent research on mentalizing abilities in neurological diseases.

Methods: An internet database search was performed to identify publications on the subject.

Results: Sixty-two publications in English corresponded to the search criteria. These publications reported impaired mentalization in several neurological disorders (e.g. epilepsy, Parkinson's disease, multiple sclerosis, dementias, traumatic brain injury).

Discussion: The results indicate that a number of neurological disorders associate with mentalizing deficit. This deficit is often present in the early stages of the diseases and has a prognostic value, which in turn emphasizes the importance of the early detection and adequate rehabilitation.
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November 2015

Minor physical anomalies are more common among the first-degree unaffected relatives of schizophrenia patients - Results with the Méhes Scale.

Psychiatry Res 2016 Mar 16;237:224-8. Epub 2016 Jan 16.

Department of Psychiatry and Psychotherapy, University of Pécs, Faculty of Medicine, Rét u.2.H, 7623 Pécs, Hungary. Electronic address:

Minor physical anomalies are external markers of abnormal brain development,so the more common appearance of these signs among the relatives of schizophrenia patients can confirm minor physical anomalies as intermediate phenotypes. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in the first-degree unaffected relatives of patients with schizophrenia compared to matched normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 relatives of patients with the diagnosis of schizophrenia and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the head and mouth regions among the relatives of schizophrenia patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that only phenogenetic variants were more common in the relatives of schizophrenia patients compared to the control group, however individual analyses showed, that one minor malformation (flat forehead) was more prevalent in the relative group. The results can promote the concept, that minor physical anomalies can be endophenotypic markers of the illness.
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http://dx.doi.org/10.1016/j.psychres.2016.01.036DOI Listing
March 2016

Acute Metabolic Effects of Olanzapine Depend on Dose and Injection Site.

Dose Response 2015 Oct-Dec;13(4):1559325815618915. Epub 2015 Nov 26.

Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA, USA.

Atypical antipsychotics (AAPs), such as olanzapine (OLZ), are associated with metabolic side effects, including hyperglycemia. Although a central mechanism of action for the acute effects on glycemia has been suggested, evidence for peripheral versus central effects of AAPs has been mixed and has not been explored for an effect of OLZ on the respiratory exchange ratio (RER). Here, we tested the hypothesis that some inconsistencies in the glycemic responses are likely a result of different doses and central sites of injection. We also compared the effects of central versus peripherally administered OLZ on the RER of unsedated rats. Third ventricle infusion of OLZ at 0.3 mg/kg caused hyperglycemia within 30 minutes, with a higher dose (1.8 mg/kg) needed to elicit a similar response in the lateral ventricles. In contrast, 3 mg/kg of OLZ was needed to raise blood glucose within 30 minutes when given intragastrically, and 10 mg/kg resulted in a prolonged hyperglycemia lasting at least 60 minutes. Third ventricle injection of OLZ significantly decreased RER after 75 minutes, whereas intragastric OLZ resulted in a faster drop in RER after 30 minutes. Since changes in glycemia were most sensitive when OLZ was infused into the third ventricle, but effects on RER were more rapidly and efficaciously observed when the drug was given peripherally, these results raise the likelihood of a dual mechanism of action involving hypothalamic and peripheral mechanisms. Some discrepancies in the literature arising from central administration appear to result from the injection site and dose.
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http://dx.doi.org/10.1177/1559325815618915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679189PMC
January 2016

Low expression of D2R and Wntless correlates with high motivation for heroin.

Behav Neurosci 2015 Dec 26;129(6):744-55. Epub 2015 Oct 26.

Department of Neural and Behavioral Sciences, College of Medicine, Pennsylvania State University.

Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.
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http://dx.doi.org/10.1037/bne0000104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658262PMC
December 2015

[Good general cognitive skills on irony understanding in schizophrenia - an fMRi study].

Psychiatr Hung 2015 ;30(3):308-17

PTE KK Pszichiatriai es Pszichoterapias Klinika, Pecs, Hungary, E-mail:

In this study we have examined a group of schizophrenia patients during the understanding of irony tasks, who had normal IQ. 14 patients and 14 healthy control subjects were included, 15 irony and 15 control tasks were invertigated during an fMRI investigation. During the contextual phase patients had shown a higher activitation in different brain regions. The healthy controls had shown deactivitation during this phase, while this couldn't be seen in the patiens group. During the irony phase healthy subjects activated brain regions known as mentalisation areas, while patients didn't. Our results can support the view, that behind schizophrenia patients mentalisation deficit the contextual phase can play the central role.
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December 2015
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