The effect of deep repetitive transcranial magnetic stimulation with an H1 coil on hopelessness in patients with major depressive disorder: A randomized controlled trial.

OBJECTIVES: To assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) with an H1 coil as a treatment for hopelessness in patients with major depressive disorder (MDD). METHODS: We conducted a randomised controlled trial in a tertiary psychiatric institution in Croatia, including patients diagnosed with MDD without psychotic symptoms and with clinically relevant hopelessness. High-frequency (18 Hz) rTMS with an H1 coil was administered over four weeks on the left dorsolateral prefrontal cortex. We examined changes in the Beck Hopelessness Scale (BHS) scores. RESULTS: We randomly assigned 51 participants to the intervention group (rTMS plus standard therapy) and 52 to the control group (standard therapy). The mean (SD) ages were 50 (12.3) and 50 (10.4) years, and 47% and 52% of the participants were females in the intervention and control groups, respectively. Following treatment, the BHS scores decreased (unadjusted bivariate analysis, p = 0.043; false discovery rate (FDR) >5%). Multivariate analysis revealed that the BHS score was reduced by 10.8% (95% confidence interval (CI: -17.8% to -3.9%) in the rTMS group and 0.7% (95% CI: 7.5% -6.1%) in the control group (p = 0.037; FDR < 5%). CONCLUSIONS: rTMS with an H1 coil improved the symptoms of hopelessness in patients with MDD.

BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling "Negative-Like" Symptoms of Schizophrenia.

We attempted throughout the NO-system to achieve the particular counteraction of the ketamine-induced resembling "negative-like" schizophrenia symptoms in rats using pentadecapeptide BPC 157, and NO-agents, NG-nitro-L-arginine methylester (L-NAME), and/or L-arginine, triple application. This might be the find out the NO-system organized therapy (i.e., simultaneously implied NO-system blockade (L-NAME) vs. NO-system over-stimulation (L-arginine) vs. NO-system immobilization (L-NAME+L-arginine)). The ketamine regimen (intraperitoneally/kg) included: 3 mg (cognitive dysfunction, novel object recognition test), 30 mg (anxiogenic effect (open field test) and anhedonia (sucrose test)), and 8 mg/3 days (social withdrawal). Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), and BPC 157 (0.01), alone and/or together, given immediately before ketamine (L-NAME, L-arginine, and combination) or given immediately after (BPC 157 and combinations). BPC 157 counteracted ketamine-cognition dysfunction, social withdrawal, and anhedonia, and exerted additional anxiolytic effect. L-NAME (antagonization, social withdrawal) and L-arginine (antagonization, cognitive dysfunction, anhedonia) both included worsening cognitive dysfunction, anhedonia, and anxiogenic effect (L-NAME), social withdrawal, and anxiogenic effect (L-arginine). Thus, ketamine-induced resembling "negative-like" schizophrenia symptoms were "L-NAME non-responsive, L-arginine responsive" (cognition dysfunction), "L-NAME responsive, L-arginine non-responsive" (social withdrawal), "L-NAME responsive, L-arginine responsive, opposite effect" (anhedonia) and "L-NAME responsive, L-arginine responsive, parallel effect" (both anxiogening). In cognition dysfunction, BPC 157 overwhelmed NO-agents effects. The mRNA expression studies in brain tissue evidenced considerable overlapping of gene overexpression in healthy rats treated with ketamine or BPC 157. With the BPC 157 therapy applied immediately after ketamine, the effect on Nos1, Nos2, Plcg1, Prkcg, and Ptgs2 (increased or decreased expression), appeared as a timely specific BPC 157 effect on ketamine-specific targets.

Pentadecapeptide BPC 157 and the central nervous system.

We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157, three very recent demonstrations that may be essential in the gut-brain and brain-gut axis operation, and therapy application in the central nervous system disorders, in particular. Firstly, given in the reperfusion, BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke, sustained brain neuronal damages were resolved in rats as well as disturbed memory, locomotion, and coordination. This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats. Secondly, there are L-NG-nitro arginine methyl ester (L-NAME)- and haloperidol-induced catalepsy as well as the rat acute and chronic models of 'positive-like' schizophrenia symptoms, that BPC 157 counteracted, and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine (dopamine agents application), MK-801 (non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration (to induce sensitivity). Thirdly, after rat spinal cord compression, there were advanced healing and functional recovery (counteracted tail paralysis). Likewise, in BPC 157 therapy, there is specific support for each of these topics: counteracted encephalopathies; alleviated vascular occlusion disturbances (stroke); counteracted dopamine disturbances (dopamine receptors blockade, receptors super sensitivity development, or receptor activation, over-release, nigrostriatal damage, vesicles depletion), and nitric oxide-system disturbances ("L-NAME non-responsive, L-arginine responsive," and "L-NAME responsive, L-arginine responsive") (schizophrenia therapy); inflammation reduction, nerve recovery in addition to alleviated hemostasis and vessels function after compression (spinal cord injury therapy). Thus, these disturbances may be all resolved within the same agent's beneficial activity, i.e., the stable gastric pentadecapeptide BPC 157.

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157.

Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats.

Pentadecapeptide BPC 157 counteracts L-NAME-induced catalepsy. BPC 157, L-NAME, L-arginine, NO-relation, in the suited rat acute and chronic models resembling 'positive-like' symptoms of schizophrenia.

In the suited rat-models, we focused on the stable pentadecapeptide BPC 157, L-NAME, NOS-inhibitor, and L-arginine, NOS-substrate, relation, the effect on schizophrenia-like symptoms. Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), BPC 157 (0.01), given alone and/or together, at 5 min before the challenge for the acutely disturbed motor activity (dopamine-indirect/direct agonists (amphetamine (3.0), apomorphine (2.5)), NMDA-receptor non-competitive antagonist (MK-801 (0.2)), or catalepsy, (dopamine-receptor antagonist haloperidol (2.0)). Alternatively, BPC 157 10 µg/kg was given immediately after L-NAME 40 mg/kg intraperitoneally. To induce or prevent sensitization, we used chronic methamphetamine administration, alternating 3 days during the first 3 weeks, and challenge after next 4 weeks, and described medication (L-NAME, L-arginine, BPC 157) at 5 min before the methamphetamine at the second and third week. Given alone, BPC 157 or L-arginine counteracted the amphetamine-, apomorphine-, and MK-801-induced effect, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization. L-NAME did not affect the apomorphine-, and MK-801-induced effects, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization, but counteracted the acute amphetamine-induced effect. In combinations (L-NAME + L-arginine), as NO-specific counteraction, L-NAME counteracts L-arginine-induced counteractions in the apomorphine-, MK-801-, haloperidol- and methamphetamine-rats, but not in amphetamine-rats. Unlike L-arginine, BPC 157 maintains its counteracting effect in the presence of the NOS-blockade (L-NAME + BPC 157) or NO-system-over-stimulation (L-arginine + BPC 157). Illustrating the BPC 157-L-arginine relationships, BPC 157 restored the antagonization (L-NAME + L-arginine + BPC 157) when it had been abolished by the co-administration of L-NAME with L-arginine (L-NAME + L-arginine). Finally, BPC 157 directly inhibits the L-NAME high dose-induced catalepsy. Further studies would determine precise BPC 157/dopamine/glutamate/NO-system relationships and clinical application.

Cognitive Distortions of Patients in the Gambling Addicts' Club - Differences with Regard to Age and Length of Treatment.

BACKGROUND: Cognitive processes are important factors in the aetiology of pathological gambling and they are always important aspect of all gambling interventions. Among other things, the gamblers' decision-making process and persistence in gambling is under the influence of their perception of the importance of knowledge/skills versus luck in different gambling activities. In this study, we examine cognitive distortions of pathological gamblers and their perceptions on the significance of luck versus knowledge/skills in different games of chance. Effects of age and length of treatment are also examined. SUBJECTS AND METHODS: A total of 65 pathological gamblers at the gambling addicts' club in Zagreb were included in the study. Cognitive distortions were measured using a modified version of the Gambling related cognitive distortions scale (Ricijas et al. 2011). Participant thoughts on the role of luck versus knowledge/skills in games of chance were measured with a questionnaire especially designed for this study. All instruments were self-assessment questionnaires and anonymously filled out during a group sessions. RESULTS: In general, results showed moderate cognitive distortions in terms of gambling beliefs, but significant perception of the importance of knowledge/skills for some games, especially sports betting and card games. Younger patients and patients in treatment for longer period have lower illusion of control. Length of treatment also seem to effect gambling-related superstition beliefs and incorrect understanding of probability, as well as importance of knowledge/skills for success in sports betting and card games. CONCLUSIONS: The results of this study lead to the indirect conclusion that length of treatment is a positive factor, which likely influences gamblers' cognitive distortions. This conclusion certainly requires additional examination using longitudinal studies, which would provide a better overview of whether these differences are in fact due to the length of treatment and also to confirm its value for future abstinence from gambling activities.

Prevalence of Pathological Gambling among Alcohol Addicts in Outpatient Treatment in the City of Zagreb: a Cross-Sectional Study.

BACKGROUND: Various types of addictions often co-occur, particularly substance and behavioral ones, which affects the clinical course of mental health disorders as well as the efficacy of therapy and rehabilitation efforts. The present study aims to explore gambling activities and possible gambling addiction among alcoholics in an outpatient treatment in the city of Zagreb. SUBJECTS AND METHODS: Gambling activities were assessed in 140 members of alcohol addiction clubs in the City of Zagreb (Croatia). Participants were undergoing treatment after being diagnosed by their psychiatrist with alcohol dependence syndrome based on ICD-10 criteria. Intensity of gambling-related problems was measured using the South Oaks Gambling Screen (SOGS), while intensity of alcohol addiction was assessed using DSM-5 diagnostic criteria for alcohol use disorder. All instruments were self-report forms and were completed using pen and paper in a group context during outpatient treatment. RESULTS: Pathological gambling was more prevalent in this clinical subsample than in general populations analysed in other studies. Alcohol addicts showing problematic or pathological gambling behaviors tended to play more highly addictive games (sports betting, slot machines, roulette). However, intensity of gambling-related problems did not correlate significantly with the intensity of alcohol addiction. CONCLUSION: These results confirm studies from other countries showing higher prevalence of problematic and pathological gambling among alcohol addicts than in the general population. Gambling behavior in our sample more often involved games with greater addictive potential. These findings suggest that alcohol addicts should be systematically screened for problematic and pathological gambling, which may improve therapeutic efficacy and rehabilitation, as well as reduce relapse in addictive behavior in general.

Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?

Selye's syndrome produced by diverse nocuous agents and "response to damage as such" means Selye's stress triad in stress coping response to reestablish homeostasis. Logically, from the gastrointestinal tract viewpoint, such organoprotective/healing response implies the angiogenic growth factors that commonly signify the healing. Thereby, the gastric pentadecapeptide BPC 157-organoprotection (huge range of beneficial effects) signifies the Selye's stress concept/stress coping response implemented in and from gastrointestinal tract, and BPC 157 as an integrative mediator that integrates the adaptive bodily response to stress. In clinical trials without side effects, LD1 not achieved, BPC 157 healing in gastrointestinal tract, and particularly the healing of the extragastrointestinal tissues (i.e., skin/tendon/ligament/muscle/bone; nerve; cornea/ brain) were referred throughout its integrative capabilities (i.e., ulcerative colitis/multiple sclerosis model equally counteracted), native in gastrointestinal tract, stability in human gastric juice (and thereby, strong efficacy and applicability), its relevance for dopamine-system function (and thereby, counteracting effects of dopamine-system dysfunction and overfunction, centrally and peripherally (mucosa maintenance); interaction with serotonin- and GABA-system)), afforded cytoprotection/adaptive cytoprotection/organoprotection (and thereby, beneficial effects on gastric and whole intestinal tract lesions and adaptation, wounds and fistulas healing, blood vessels, somatosensory neurons, NSAIDs-side effects (including also pancreas, liver, brain lesions, and blood disturbances, prolonged bleeding, thrombocytopenia, thrombosis)). Further, we combine such gut-brain axis and the NO-system where BPC 157 counteracts complications of either L-NAME application (i.e., various lesions aggravation, hypertension) or Larginine application (i.e., hypotension, prolonged bleeding, thrombocytopenia). Also, BPC 157 particularly affects genes functions (i.e., Fos, c-Jun, Egr-1), all together suggestive for an indicative generalization. Thus, we could suggest gastric pentadecapeptide BPC 157 and BPC 157 induced-organoprotection as integrative mediator that integrates the adaptive bodily response to stress, and thereby practically applied in further therapy and in effective realization of Selye's stress response.

Preoperative preparation of alcohol and psychoactive substances-addicted patients.

Proper diagnosis of psychoactive substance abuse and addiction, as well as acute intoxication, withdrawal syndrome and overdosing are of great importance in patients who are preparing for surgical intervention. There are some specific details in their preoperative preparation whether they underwent emergency or elective surgery. Good knowledge of the characteristics of psychoactive substance abuse and addiction, interaction of psychoactive substances and anesthetics and any other drugs that could be used in the perioperative period is important especially for anastesiologist. In this work we present key issues for recognizing theese patients as well as some guidelines for adequate preoperative preparation and postoperative care.

Relationship between anger, alcoholism and symptoms of posttraumatic stress disorders in war veterans.

PURPOSE: Studies among veterans indicate that veterans with posttraumatic stress disorder (PTSD) express anger, hostility and aggression as well as alcohol and substance abuse more then veterans without PTSD. The aim of this study was to analyze the relationship between anger, use of alcohol and symptoms of PTSD in war veterans in Bosnia and Herzegovina (B&H). METHOD: Comparing a group of veterans (n = 54) with PTSD who use alcohol and a group of veterans (n = 46) who do not use alcohol, the analyzed were dimensions of anger related to PTSD symptoms and alcohol usage. Medical records of patients treated at the Department for Psychiatry in Tuzla, B&H, Harvard Trauma Questionnaire (HTQ)--version for Bosnia and Herzegovina, State-Trait Anger Expression Inventory (STAXI), Structured Clinical Diagnostic Interview (SCID-I) were used in this study. The basic socio-demographic data were also collected. RESULTS: A significant correlation is found between alcohol usage, and state and trait of anger (P < 0.001), angry temperament (P = 0.001), anger-in expression (P < 0.001), anger-out expression (P < 0.001), and anger control (P < 0.001). PTSD hyperarousal cluster symptoms were significantly correlated to state anger, anger-in expression (P < 0.05), and use of alcohol (P = 0.010). CONCLUSION: The results indicate that there is a significant correlation between PTSD arousal symptom with anger dimensions, as well as between anger dimensions and use of alcohol in war veterans with PTSD.

Relationship between serum lipid concentrations and posttraumatic stress disorder symptoms in soldiers with combat experiences.

The aim of our study was to assess concentrations of serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides in soldiers with combat-related posttraumatic stress disorder (PTSD), in comparison with combat-experienced soldiers without PTSD. The second aim of our study was to explore the relationship between PTSD symptoms such as re-experiencing, avoidance, increased arousal, and serum lipid levels. In 53 soldiers with combat-related PTSD and 49 with combat experiences without PTSD, serum cholesterol, LDL-C, HDL-C, and triglycerides were assayed by an enzyme-assay method. Soldiers with combat-related PTSD were found to have significantly higher concentrations of cholesterol (P = 0.001), LDL-C (P = 0.002), and triglycerides (P = 0.001) than soldiers without current PTSD. HDL-C was statistically lower (P < 0.001) in soldiers with combat-related PTSD than in those without PTSD. A positive correlation was found between increased arousal and cholesterol (r = 0.464; P = 0.039), or LDL-C (r = 0.479; P = 0.021) concentrations.

Agresión en el Trastorno de Estrés Postraumático comórbido con Dependencia Alcohólica

El objetivo de este estudio es el de investigar la dependencia del alcohol en soldados profesionales de combate con Trastorno de Estrés Postraumático (PTSD) relacionado con el incremento de la agresión. Se entrevistaron dos grupos de soldados de combate profesionales, utilizando entrevistas clínicas estructuradas basadas en el criterio DSM IV para PTSD crónico (N = 40), y PTSD coexistente con dependencia al alcohol (N = 40). La escala de ratios para la agresión A-87 se utilizó para explorar el nivel de agresión entre estos grupos. Los soldados profesionales de combate con PTSD comórbido con una dependencia al alcohol, mostraron mayores niveles de agresión verbal que aquellos soldados que presentaban únicamente PTSD, (54,97+- 8,62 vs 49,47 +- 12,76; t = 2,19; p < 0,05), así como conductas manifiestas de agresión física (41,75+- 9.80 vs 35,62 +- 10,80; t = 2,96; p < 0,05). La comorbilidad con dependencia al alcohol podría jugar un papel en cuanto a los niveles de agresión en las experiencias de PTSD crónicos especialmente al presentarse la agresión. (AU)

Comorbid alcohol addiction increases aggression level in soldiers with combat-related post-traumatic stress disorder.

The aim of this study was to compare aggressive behavior in soldiers with combat-related post-traumatic stress disorder (PTSD), PTSD comorbid with alcohol addiction and alcohol addiction only. Three groups of male combat experienced soldiers with PTSD (n=43), PTSD comorbid with alcohol addiction (n=41) and alcohol addiction (n=39) were compared by Aggression rating scale A-87. PTSD was diagnosed according to DSM-IV criteria and Watson's PTSD rating scale. Alcohol addiction was diagnosed according to DSM-IV criteria and CAGE Questionnaire. Combat-experienced soldiers with alcohol addiction as well as soldiers with combat-related PTSD comorbid with alcohol addiction have a high level of verbal latent aggression (VLA), (F=26.65; P<0.001), physically latent aggression (PLA), (F=37.86; P<0.001), indirect aggression (INA), (F=56.94; P<0.001), verbal manifest aggression (VMA), (F=18.35; P<0.001), and physically manifest aggression (PMA), (F=43.22; P<0.001), vs. soldiers with combat-related PTSD without comorbid conditions. Alcohol addiction is a severe factor in increasing aggression levels in soldiers with PTSD.