ABSTRACT
OBJECTIVES: This study was designed to find possible effect of pregnancy and parturition on spatial memory, especially in relation to levels of estrogen during the third trimester and postpartal period in rats. METHODS: 25 female Sprague Dawley rats were divided into pregnant group (N=14) and control group (N=11). Changes in spatial memory during 6 weeks including third trimester and postpartal period were measured using Morris water maze. Time to reach the platform in the maze was indicator of spatial memory. Serum estrogen level was measured on 1 week before delivery, postpartal day 1, and day 14. RESULTS: Both groups showed gradual improvement in performance by trial days and weeks, but no significant difference was found between the two groups. However in the third trimester, pregnant group showed a trend of less achievement on 3 days of learning than control group. Serum estrogen levels did not differ significantly between groups over the 6 weeks of period. However there was positive correlation between serum estrogen level on postpartum day 1 and time to reach platform on postpartum week 2, and negative correlation between estrogen level on postpartum day 14 and latency to the platform on postpartum week 5. CONCLUSION: These results imply that changes in the serum estrogen level may have dual effects on the spatial learning in peripartal period. It is suggested that decline in cognitive function might occur either by failure of rapid decrease of estrogen, immediately after parturition, or retarded restoration of estrogen in later postpartal period.
Subject(s)
Animals , Female , Humans , Pregnancy , Rats , Estrogens , Learning , Memory , Parturition , Postpartum Period , Pregnancy Trimester, Third , Rats, Sprague-DawleyABSTRACT
OBJECTIVES: There are a number of preceding epidemiological studies reporting gender differences in the genetic etiology of alcohol dependence. The author investigated gender difference in the frequencies of ADH2 and ALDH2 genoypes between the patients with alcohol dependence and normal control. METHODS: The subjects were 141 alcohol dependent patients (104 males, 37 females) and 138 normal control (79 males, 59 females). The frequencies of 1/1 and 1/2+2/2 (2+ afterward) genotypes for ADH2 and ALDH2 were investigated in male and female between alcohol dependence and normal control group. DNA was extracted from WBC in peripheral venous blood and PCR-RFLP method was used out for genotyping. RESULTS: First, the frequency of ADH2 1/1 genotype was significantly higher in alcohol dependent patients than normal control in both genders. Second, while there was no gender difference in the frequency of ADH2 1/1 genotype in normal controls, in the patient group however, the frequency was significantly higher in females than males. Third, in male subjects with alcohol dependence, the frequency of ALDH2 1/1 genotype was significantly higher than in male normal control subjects. On the other hand, in female subjects with alcohol dependence, the frequency of ALDH2 2+ genotype was significantly higher than in female normal control subjects. CONCLUSION: These results suggest that while the risk of alcohol dependence is predominantly affected by ALDH2 1/1 genotype in male, the female ADH2 1/1 genotype is mainly associated with the risk of alcohol dependence. This means that there are gender differences in the genetic etiology of alcohol dependence.
Subject(s)
Female , Humans , Male , Alcoholism , DNA , Epidemiologic Studies , Genotype , HandABSTRACT
OBJECTIVES: We investigated the effects of naltrexone on acute alcohol response, stimulant and sedative, in healthy social drinkers using two doses of alcohol intake. METHODS : Twenty four healthy male medical students were voluntarily participated. The experimental method was crossover design. Subjects received 25 mg/day or 50 mg/day of naltrexone on the experimental days. Biphasic Alcohol Effects Scale (BAES), alcohol craving, and blood alcohol concentration (BAC) were measured before drinking and at 15, 30, 45, 60, 90, and 120 min after drinking. RESULTS : 1) Group of 0.6 mg/kg of alcohol intake. When the scores of stimulative subscale of BAES were compared between the naltrexone and control group, the scores were significantly lower in the naltrexone group at 15 and 90 min after drinking. Alcohol induced sedative effect was significantly higher in the naltrexone group at 90 min after drinking. The alcohol induced alcohol craving at 45 and 60 min after drinking was significantly lower in the naltrexone group as compared to the control. 2) Group of 0.3 mg/kg of alcohol intake. The alcohol induced stimulative effect evident in the control group seen in the time span of 15 to 45 min after drinking was not seen in the naltrexone group. The increase of alcohol induced alcohol craving noticed at 30 min after drinking in the control group was not seen in the naltrexone group. BAC at 15 min after drinking was lower in the naltrexone group compared to the control. CONCLUSION : Naltrexone is suggested to attenuate stimulative effect, to intensify sedative effect, and to block alcohol induced alcohol craving. These triple actions might be utilized for treatment and prevention of relapse of alcohol dependence.
Subject(s)
Humans , Male , Alcoholism , Cross-Over Studies , Drinking , Hypnotics and Sedatives , Naltrexone , Recurrence , Students, MedicalABSTRACT
OBJECTIVES: This study investigated the validity of positive-negative dichotomy model by comparing the differences of neurocognitive function in the specific symptom subgroups of schizophrenia. METHODS: Factor analysis was performed on 14 items of the Positive and Negative Syndrome Scale (PANSS) among 71 inpatients with schizophrenia. All patients were assigned to one of specific symptom subgroups based on a ratio score and compared the neurocognitive distinction of each subgroups with normal control group, which was composed of 60 healthy persons without psychiatric illness. Neurocognitive functions include sustained attention, sensory register, executive function, attention and concentration, and verbal memory and learning obtained using Degraded Stimulus Continuous Performance Test, Span Apprehension Task, Wisconsin Card Sorting Test, Digit Span, and Rey Auditory Verbal Learning Test respectively. RESULTS: Three factors, positive, negative and disorganized, were yielded from factor analysis on 14 items of the PANSS. Three symptom subgroups showed the differential neurocognitive profiles. Disorganized symptom subgroup showed significant deficits in the sustained attention, sensory register, executive function, attention and concentration, and verbal memory and learning compared with the normal controls. Negative symptom subgroup showed significant deficits in the sustained attention, sensory register, executive function, and verbal memory and learning. Positive symptom subgroup showed significant deficits only in the sustained attention and sensory register compared with the normal controls. No significant differences were noted in the sustained attention, sensory register, attention and concentration, and verbal memory and learning among three symptom subgroups. But the disorganized symptom subgroup showed a significant deficit in the executive function compared to the positive symptom subgroup. CONCLUSIONS: These results support that three symptom dimensions including disorganization may be more valid than the positive-negative symptom dichotomy in the dimensions of schizophrenic symptoms.
Subject(s)
Humans , Executive Function , Factor Analysis, Statistical , Inpatients , Learning , Memory , Schizophrenia , Verbal Learning , WisconsinABSTRACT
OBJECTIVES: Previous studies have shown that the endogenous opioid system, which plays an important role in drinking behavior, might be related to the genetic etiology of alcohol dependence. And a recent study reported that the affinity of micro opioid receptor, which is closely related to the endogenous opioid system activity, is affected by the genotype of micro opioid receptor gene (OPRM1) A118G. The present study examined the association of the genotype of OPRM1 A118G with alcohol dependence in Koreans. METHODS: The author studied the genotype of OPRM1 A118G in 112 Korean patients with alcohol dependence and 140 healthy Korean control subjects. RESULTS: 1) A statistically significant increase in A/G or G/G genotype of OPRM1 A118G was observed in patients with alcohol dependence (67.0%) compared to the controls (51.4%). 2) Among patients with alcohol dependence, no significant difference in OPRM1 A118G polymorphism was observed relative to the age at which drinking started, the age of onset of alcohol-related problems, the age of first admission to psychiatric hospital for alcohol-related problems, the family history of alcohol dependence in the first-degree relatives or of severe alcohol withdrawal symptoms. But the frequency of A/G or G/G genotypes of OPRM1 A118G was significantly higher in those who drank 17 days or more per month in the previous year (80.8%) than in those with fewer days of drinking (56.5%). CONCLUSION: These results suggest that A/G or G/G genotypes of micro opioid receptor gene A118G are important genetic factors in the etiology of alcohol dependence.
Subject(s)
Humans , Age of Onset , Alcoholism , Drinking , Drinking Behavior , Genotype , Hospitals, Psychiatric , Receptors, Opioid , Substance Withdrawal SyndromeABSTRACT
OBJECTIVE: The aim of this study is to determine effects of nefazodone on depression, anxiety, sleep and sexual function in depressive patients. SUBJECTS AND METHODS: This is an open, non-comparative, multi-center study. Antidepressant and other clinical effects of nefazodone were evaluated in 230 patients of 26 centers, aged 14 years or more, who met DSM-IV criteria to major depressive disorder or dysthymic disorder and didn't have other psychiatric disorders and were physically healthy. The clinical efficacy was assessed at week 1, 2, 4 and 8 using Clinical Global Improvement (CGI), Hamilton Depression Scale (HAM-D), Beck Depression Inventory (BDI), State and Trait Anxiety Inventory-State Anxiety (STAI-SA). Other clinical effects were assessed with Weekly Sleep Questionnaire, Sexual Functioning Questionnaire and GHQ-QOL-12, a scale for quality of life. Adverse drug reactions were checked with a questionnaire. Post-treatment effects of drug were compared with pre-treatment baseline condition. RESULTS: The response rates by Clincal Grobal Improvement and HAM-D after 8 weeks treatment were 62.4% and 75.2% respectively. Comparing to baseline, nefazodone was proved to have significantly higher antidepressant and antianxiety effects in depressive patients and it improved also sleep, sexual functions and quality of life. Both patients and physicians satisfied with the effects of drug. Adverse drug reactions were a few and not serious, and most of them disappeared as treatment continued. CONCLUSION: These results suggest that not only nefazodone has antidepressant effects and antianxiety effects, but also it improves sleep disturbance, sexual dysfunction and the quality of life in depressive patients. Adverse drug reactions were a few and not serious.
Subject(s)
Humans , Anti-Anxiety Agents , Anxiety , Depression , Depressive Disorder, Major , Diagnostic and Statistical Manual of Mental Disorders , Drug-Related Side Effects and Adverse Reactions , Dysthymic Disorder , Quality of Life , Surveys and QuestionnairesABSTRACT
OBJECTIVES: For the relapse prevention in alcohol dependence, a lot of studies suggested that combined administration of two or more drugs which have different mechanism of action is more effective than each drug alone. In order to investigate the effectiveness of combined administration of naltrexone and acamprosate in comparison with naltrexone alone, this study was carried out by comparing the amount of alcohol intake in C57BL/6 mice co-administered with naltrexone and acamprosate with that in C57BL/6 mice with naltrexone alone. METHODS: In 42 C57BL/6 mice in the state of alcohol dependence, naltrexone 0.025mg/kg or 1.0mg/kg alone or with acamprosate 50mg/kg or 200mg/kg were administrated for ten days. The amounts of alcohol consumption for 2 hour, water consumption for 22 hours, and food intake for 24 hours were measured. RESULTS: 1) A significant reduction of alcohol intake for 2 hours was observed when the mice were treated with naltrexone 0.025mg/kg or 1.0mg/kg and acamprosate 50mg/kg or 200mg/kg simultaneously compared with naltrexone 0.025mg/kg or 1.0mg/kg alone. This effect was significant on the eighth and tenth days of drug administration. 2) Naltrexone administration of 1.0mg/kg was significantly more effective than that of 0.025 mg/kg in reducing alcohol intake from the second day of drug administration up to the tenth day. 3) No significant difference was revealed between the effect of naltrexone alone and that of naltrexone with acamprosate on 22 hour water consumption and 24 hour food intake. CONCLUSION: From these results, it is suggested that the effect of combined treatment with naltrexone and acamprosate is superior to that of naltrexone alone in prevention of relapse in alcohol dependence.
Subject(s)
Animals , Mice , Alcohol Drinking , Alcoholism , Drinking , Eating , Naltrexone , RecurrenceABSTRACT
In order to evaluate whether Wisconsin Card Sorting Test(WCST) could be used to detect the vulnerability markers of schizophrenia, three groups such as offsprings of schizophrenic patients(n=28), offsprings of alcoholic patients(n=18), and offsprings of psychiatrically normal persons(n=41) were examined for their concept formation and abstract thinking by means of WCST.The results were as follows; 1) No significant differences were noted in all variables of the WCST such as number of totol administered trials, total correct response %,total error response $,perseverative response %,perseverative error response %,nonperseverative error response %,conceptual level response %,number of completed category,number of trials to complete 1st category,number of failure to maintain a set,and learning to learn among three groups. 2) There was no difference in the number of cases with extreme low WCST total correct % of lower 10% of the normal controls among three groups. These results suggest that Wcst could be an ineffective instrument for using to detect the vulnerability markers of schizophrenia.
Subject(s)
Humans , Alcoholics , Concept Formation , Learning , Schizophrenia , Thinking , WisconsinABSTRACT
In an attempt to obtain the basic data for mental disability evaluation in psychiatric casualties by traffic accidents, 88 cases referred fiom the court for the purpose of mental disability evaluation for 3 years from 1994 to 1996 were surveyed. The results are summarized as follows: 1) Among the 88 cases, 58 cases(65.9%) were male and 30(34.1%) were female. Cases with low educational and socioeconomic levels outnumbered those with high educational and socioeconomic levels. More than half of the cases were in socially active group with ages of 21 to 50 years. 2) At the time of accidents, 71.6% of the whole cases were diagnosed as cerebral contusion, which was the most common diagnosis. The next common diagnoses were skull fracture(36.4%), brain hemorrhage(33.0%), brain hematoma(26.1%), cerebral concussion(12.6%), and axonal injury(10.2%) in order of frequency. In 9.1% of the cases there was no definite evidence of head injury was found. 3) During the period of mental disability evaluation, the most common symptom was cognitive symptom(85.2%), and the next common symptoms were somatic(83.0%), behavioral(69.3%), and affective(58.0%) ones in order of frequency. On the other side, the most common psychopathology recognized by the psychiatrists was affective symptom, which was present in 80.9% of the cases manifested during the period of evaluation, and the next common psychopathologies were behavioral(77.3%), cognitive(63.6%), and somatic(40.9%) symptoms in order of frequency. 4) Nearly half(48.8%) of the whole patients manifested psychiatric symptoms such as cognitive, affective, behavioral, and somatic symptoms between the first and sixth months after traffic accidents. Only 9.1% of the cases developed psychiatric symptoms after six months of traffic accidents. Meanwhile, 61.4% of the cases were never given psychiatric treatments despite the presence of psychiatric symptoms, and 23.5% of the cases given psychiatric treatments visited psychiatrists after six months of symptom development. 5) All of the cases took neuroimaging studies such as brain CT or MRI and EEG during the feriod of mental disability evaluation. In 47.7% of the cases there were abnormal findings in neuroimaging studies among which encephalomalacia was the most frequent. The next abnormal findings were brain atrophy, axonal injury, cyst, and so on in order of frequency. On the other hand, in 86.4% of the cases EEG findings were within normal limit. 6) In 95.5% of the cases, mental disorders were confirmed, among which personality change due to head trauma was the most common, and the next common mental disorders were dementia due to head trauma, adjustment disorder, depressive disorder due to head trauma, postconcussional disorder, posttraumatic stress disorder, and so on in order of frequency. More than one third of the cases(38.1%) given psychiatric diagnoses were considered to need continuous psychiatric treatments at the time of mental disability evaluation. 7) Posttraumatic decline in intelligence tended to be affected by loss of consciousness and delirium, but not by skull fracture and brain surgery. In brain imaging and EEG studies performed during the period of mental disability evaluation, posttraumatic decrease in intelligence tended to be influenced by abnormal findings on brain imaging, but not EEG findings.
Subject(s)
Female , Humans , Male , Accidents, Traffic , Adjustment Disorders , Affective Symptoms , Atrophy , Axons , Brain , Contusions , Craniocerebral Trauma , Delirium , Dementia , Depressive Disorder , Diagnosis , Disability Evaluation , Electroencephalography , Encephalomalacia , Hand , Intelligence , Magnetic Resonance Imaging , Mental Disorders , Neuroimaging , Psychiatry , Psychopathology , Skull , Skull Fractures , Stress Disorders, Post-Traumatic , UnconsciousnessABSTRACT
OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. METHOD: This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points: at baseline, and 1,2,4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. RESULTS: 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action: a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. CONCLUSIONS: This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.
Subject(s)
Humans , Dyskinesias , Dystonia , Electrocardiography , Hospitalization , Hospitals, University , Parkinsonian Disorders , Risperidone , Schizophrenia , Vital Signs , Weights and MeasuresABSTRACT
In order to study the possible vulnerability in the markers of schizophrenia, offsprings of the schizophrenic parents(n=28), offsprings of the alcohol dependent parents(n=18), and offsprings of the psychiatrically normal persons(n=41) were examined for their sustained attention and sensory register by means of Continuous performance test(CPT) and Span apprehension task(SPAN) respectively. The results were as follows: 1) The offsprings of the schizophrenic parents showed a significant deficit in the sustained attention as manifested in the data of CPT by significantly lower hit rate and sensitivity, compared with the offspring of the alcohol dependent parents and those of the psychiatrically normal persons. No difference was evident in the false alarm rate and response bias among three groups. There was no difference in all variables of the CPT between the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. 2) The deficit in the sustained attention as revealed by lower hit rate and sensitivity was not apparent in the first part of the CPT. However it emerged and aggravated itself as the test continued in the offsprings of the schizophrenic parents only. 3) Proportion of subjects falling in the extreme low sensitivity of lower 10% of the normal controls was significantly higher in the offsprings of the schizophrenic parent group as compared with the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons with a rate of 29%, 17%, and 10% respectively. 4) No significant difference was noted in all variables of MMPI among normal controls, index group, and the extreme low CPT sensitivity subgroup of index group. 5) The offsprings of the schizophrenic parents showed a significantly delayed response in the time to correct and incorrect response in SPAN compared to offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. No difference was evident in the number of correct response, number of incorrect response, and number of no response among three groups. There was no difference in all variables of the SPAN between the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. These results suggest that a subgroup of the offsprings of schizophrenic parents may suffer from the deficit in the sustained attention which may be a vulnerability marker of schizophrenia.
Subject(s)
Humans , Electronic Data Processing , Bias , MMPI , Parents , SchizophreniaABSTRACT
OBJECTIVES: This study was aimed at investigating the effect of haloperidol on alcohol craving in patients wih alcohol dependence. METHODS: Eighteen patients with alcohol dependence were divided randomly into two groups of nine patients each: one haloperidol group and the other, placebo group. The medication for each group was done for 14 days. Alcohol craving and difficulty in resisting drinking were measured on day 1 and day 14, each consisting of a series of four assessments. Assessment 0 was basal levels. Assessment 1 was made 3 hours after medication. Assessment 2 was made after alcohol intake in a dose of 0.4gm of 100% alcohol/kg body weight and assessment 3 was done after the second alcohol intake in the same amount. RESULTS: The results were as follows: 1) With acute treatment, placebo group showed a significant increase in alcohol craving whereas haloperidol group did not show any change after the first and second alcohol intake. 2) With chronic treatment, both groups showed significant increase in the alcohol craving after alcohol intake. 3) Haloperidol did not increase difficulty in resisting drinking after acute treatment, however, with chronic treatment, it resulted in a significant increase of the difficulty in resisting drinking. CONCLUSIONS: From these results, the authors suggest that an acute treatment of haloperidol lowers alcohol craving in patients with alcohol dependence, but the effect does not maintain itself with chronic treatment.
Subject(s)
Humans , Alcoholism , Body Weight , Drinking , HaloperidolABSTRACT
In light of recent reports of the effectiveness of Radix puerariae in the alcoholics and recent formulation of a hypothesis that craving far alcohol In the alcohol-dependent individual is mediated by a limbic circuit involving the fronto-thalamic and fronto-striatoaccumbal region, the authors studied the effect of Radix puerariae on craving for alcohol and cerebral blood flow(rCBF) of these regions. The subjects were hospitalized patients with alcohol dependence recovered from acute intoxication and withdrawal symptoms. On the first day of experiment, rCBF in the areas of caudate nuclei, thalamus and orbitofrontal cortices was measured by Single-Photon Emission Computed nomography. On the third day, the same procedure was repeated artier intake of a small priming dose of alcohol. Radix puerariae in dose of 12gm/day for 10 days was given from fourth day of experiment to the thirteenth day and on the eleventh and thirteenth days, the measurements of rCBF were repeated in the same method as in the first and third day, respectively. Immediately before measurements of the rCBF in each experiment, craving far alcohol was measured by means of Visual Analogue Scale. The results were as follows: 1) Before the treatment of radix puerariae, the alcohol-dependent patients developed a significant alcohol-induced alcohol craving and a concomitant increase of rCBF in the right head of caudate nucleus. 2) Radix puerariae significantly lowered alcohol crating and significantly increased rCBF In the right head of caudate nucleus and the left orbitofrontal cortex in alcohol-free, basal condition. 3) After the treatment of radix puerariae, the rCBF after alcohol intake in bilateral caudate nuclei and bilateral hemithalami was significantly decreased. 4) Radix puerariae did not induce post-alcohol craving for alcohol and significantly decreased post-alcohol rCBF in bilateral caudate nuclei. From these results, it is suggested that Radix puerariae decreases basal alcohol craving in the alcohol-dependent patients, and further that there ma!~ exist a significant association between these changes of alcohol craving and concomitant changes of rCBF in the limbic striatim, especially caudate nucleus.
Subject(s)
Humans , Alcoholics , Alcoholism , Caudate Nucleus , Head , Pueraria , Substance Withdrawal Syndrome , Thalamus , Tomography, Emission-Computed, Single-PhotonABSTRACT
Recurrent mood disorders show tendencies toward cycle acceleration over time-shorter and shorter well intervals belween successive episodes. On the other hand, clinical findings suggest that psychosocial stresses ore impl icated more prominently in early episodes of mood disorders, whereas less prominent stressors or conditioned behavioral factors are associated with the onset of later episodes. The dual models of behavioral sensitization and kindling may help to explain the pattern of apparent clinical course in th natural history of mood disorders and to link older psychoanclytic and neurobiologic concepts of illness evaluation. The unified approach suggests that psychosocial precipitants are involved in initial episodes, but later ones occur more autonomously : both the stresses and episodes themselves may leave behind changes in the individual's neurobiology by affecting gene expression. From the standpoint of treatment the dual models place a high premium on effective early pharmacologic interventions and their long term maintenance, and support the combination of psychotherapeutic and pharmacologic interventions, accepting the usefulness of psychodynamic or cognitive therapy.