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Biomedical subjects

M Linnoila

Publications and source records attributed to M Linnoila.

At least 55 records · Page 3Linked to original sources
PubMed1998

In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates.

OBJECTIVE: Studies on brain serotonin metabolism in human and nonhuman primates have indicated that dysfunction of serotonin transmission may play a role in the biological vulnerability to dependence on alcohol. Among young men, low sensitivity to alcohol intoxication predicts subsequent alcohol abuse and dependence. METHOD: The authors used single photon emission computed tomography and the radioligand [(I)123]beta-CIT ([(I)123]methyl 3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the availability of serotonin transporters in 11 male rhesus monkeys, and the monkeys were genotyped for a functional polymorphism of the serotonin transporter gene. The 11 monkeys had experienced parental separation after birth; their behavior and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in CSF had been assessed regularly. RESULTS: In the 5-year-old monkeys, there was a significant negative correlation between beta-CIT binding to serotonin transporters in the brainstem and 5-HIAA concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were less sensitive to alcohol-induced intoxication. The genetic constitution of the serotonin transporter promoter gene did not significantly contribute to the availability of brainstem serotonin transporters as measured by beta-CIT binding. CONCLUSIONS: In adult nonhuman primates who underwent early developmental stress, variables indicating a low serotonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans.

Adult↗
PubMed1997

Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior. A nonhuman primate model investigating genetic and environmental influences on neurotransmission.

We have used nonhuman primates to examine developmental and behavioral correlates of CNS serotonergic activity, as measured by concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). These studies show that interindividual differences in CNS serotonin turnover rate exhibit traitlike qualities and are stable across time and settings, with interindividual differences in CSF 5-HIAA concentrations showing positive correlations across repeated sampling. Primates with low CNS serotonergic activity exhibit behaviors indicative of impaired impulse control, unrestrained aggression, social isolation, and low social dominance. Maternal and paternal genetic influences play major roles in producing low CNS serotonin functioning, beginning early in life. These genetic influences on serotonin functioning are further influenced by early rearing experiences, particularly parental deprivation.

Animals↗
PubMed1997

Effect of alcoholism on the incidence of lactate-induced panic attacks.

BACKGROUND: Chronic alcohol use is associated with higher than expected rates of panic disorder. METHODS: To study the relationship between alcoholism and panic disorder, we administered the panicogenic agent, sodium lactate, to 26 alcoholics with either panic disorder or frequent panic attacks (ALCPAN), 20 nonalcoholics with panic disorder (PAN), 14 alcoholics without a history of panic attacks, and 14 healthy volunteers. RESULTS: PAN were significantly more likely to have a lactate-induced panic attack (65%) than ALCPAN (23%). ALCPAN who had the onset of panic attacks prior to alcoholism also had a reduced frequency of lactate-induced panic attacks (26.7%) compared to PAN. CONCLUSIONS: There is a reduced incidence of lactate-induced panic attacks in ALCPAN. This reduction does not appear to be explained by the relative onset of panic attacks to alcoholism. The role of excessive alcohol consumption in the decreased frequency of lactate-induced panic attacks seen in ALCPAN needs further study.

Adult↗
PubMed1997

Rhesus macaques with high CSF 5-HIAA concentrations exhibit early sleep onset.

The relationship between central nervous system serotonergic activity, as reflected by cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and sleep/wakefulness behavior was investigated in socially housed, juvenile rhesus macaques. Two cohorts of rhesus monkeys (Macaca mulatta), numbering 42 subjects (seventeen 39-month-olds and twenty-five 20-month-olds) were observed in their home cages between 21.30 h and 23.30 h for 10 nights using an infrared night scope. Over each 90-min observation period, the following states were recorded every 5 min using a scan sampling procedure: Sleep, Drowsy, Passive-awake and Active. After more than one quarter of the animals in the group had fallen asleep, states were recorded as they occurred. Six weeks prior to the collection of the behavioral data, a sample of cisternal CSF was obtained to assay for 5-HIAA concentrations. With cohort effects statistically controlled, there was a negative correlation between latency to fall asleep and CSF 5-HIAA concentrations (i.e., subjects with high CSF 5-HIAA concentrations were more likely to fall asleep early). Subjects with low CSF 5-HIAA concentrations were also more active during the daytime hours. Subjects who fell asleep first were, on average, also less active during nighttime hours. The positive correlation between CSF 5-HIAA and sleep onset was not a result of social status since there was no correlation between social dominance rank and time of sleep onset. These results support the hypothesis that the serotonergic system may play a role in sleep onset and possibly in the regulation of diurnal activity rhythms in non-human primates.

Animals↗
PubMed1997

CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season.

This study examines sexual behavior, serotonin turnover in the central nervous system, and testosterone in free-ranging non-human primates. Study subjects were 33 young adult male rhesus macaques (Macaca mulatta) living in naturalistic social groups on a 475-acre South Carolina barrier island. Blood and cerebrospinal fluid (CSF) samples were obtained during random trappings, and the subjects were located for observation by radio telemetry. Quantitative behavioral samples totaling 203 observation hours were taken during two mating seasons (September through January) in 1994 and 1995. Control observations (65 h) on 13 subjects were also taken during the non-mating seasons in 1994 and 1995. The results indicate that CSF 5-hydroxyindoleacetic acid (5-HIAA), CSF testosterone, and plasma testosterone concentrations increase significantly during the mating season. During the mating season, there were significant increases in high intensity aggression, low intensity aggression, grooming behavior, and heterosexual mounting. In the mating season, CSF 5-HIAA was significantly correlated with several sociosexual behaviors: consorts per hour, heterosexual mounts per hour, and inseminations per hour. In contrast to previous findings from the non-mating season, CSF 5-HIAA was not correlated with any measures of aggression or sociality, although during consorting, CSF 5-HIAA was positively correlated with grooming. From these findings, we conclude that the lack of correlation between intense and severe aggression and CSF 5-HIAA in the mating season may reflect the use of high intensity aggression in 'normative' male-male competition over access to reproductively active females. We also conclude that CNS serotonin turnover is positively correlated with sexual competence, i.e. males with low CSF 5-HIAA concentrations are less sexually competent than males with higher concentrations.

Aggression↗
PubMed1997

Effects of m-chlorophenylpiperazine on regional brain glucose utilization: a positron emission tomographic comparison of alcoholic and control subjects.

m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonist used extensively in psychiatric research. Alcoholics show blunted neuroendocrine responses to mCPP, and in some settings mCPP can induce craving for alcohol, particularly among early onset alcoholics. We used 2-[18F]-2-deoxy-D-glucose positron emission tomography to examine the effects of intravenously administered mCPP (0.08 mg/kg) on brain glucose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statistically with a Gaussian random field-based method. Among healthy volunteers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilaterally, the left nucleus accumbens, the head of the caudate nucleus bilaterally, the anterior and medial-dorsal nuclei of the thalamus bilaterally, the middle frontal gyrus, the left insular cortex, the left middle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate than it did in healthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almost no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These results suggest that a serotoninergic challenge activates basal ganglia circuits involving orbital and prefrontal cortices among healthy volunteers but that the response of these circuits is blunted among alcoholics.

Adult↗
PubMed1997

Serotonin in early-onset alcoholism.

This chapter examines current, common schemes to subgroup alcoholics to arrive at relatively homogeneous groups of patients to facilitate psychobiological and molecular genetic studies. Early-onset, male-limited alcoholism is commonly associated with antisocial personality disorder or antisocial behavioral traits. It is often preceded by early-onset aggressiveness, which is followed by conduct disorder. Early-onset alcoholism among men is associated with low central serotonin turnover rate. The data concerning platelet MAO activity and serotonin uptake to platelets among early-onset alcoholics are conflicting. Recent molecular genetic and brain imaging studies on early-onset alcoholics are preliminary but appear very promising.

Aggression↗
PubMed1997

Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers.

Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated possible relationships between DNA polymorphisms in the tryptophan hydroxylase (TPH) and catechol-O-methyltransferase (COMT) genes and CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 66). Lower CSF 5-HIAA levels were found in men with the TPH U allele (p = 0.005), but not in women. A similar but less significant pattern was observed for CSF HVA. No relationship was found between the TPH polymorphism and CSF MHPG. COMT genotypes did not relate significantly to MM concentrations. The results suggest that TPH genotypes participate differentially in the regulation of serotonin turnover rate under presumed steady state in the central nervous system of men. Due to the uncertain functional relevance of the DNA polymorphism investigated and the many calculations performed, the results should be interpreted with caution until replicated.

Adult↗
PubMed1997

Suicidal behavior among Finnish fire setters.

Histories of serious suicide attempts and slashing were investigated among Finnish fire setters. Medical and criminal records of 304 fire setters were examined to compare those who had attempted suicide with those who had not, and those who had slashed themselves with those who had not using biological, diagnostic, and demographic variables. Major mood disorders, father's alcoholism, and suicidal motive of fire setting (self-immolation) were significantly associated with suicide attempts. Paternal violent alcoholism, father's criminality, and suicidal motive of fire setting were significantly associated with slashing. Among fire setters, non-lethal slashing is a predictor of serious suicidality. Associations between psychiatric diagnoses, family history, and suicidality among fire setters are similar to those reported for suicidal patients with mood and substance abuse diagnoses. Therefore, studying fire setters, who exhibit an extremely high incidence of suicidal behavior, is an effective way to elucidate psychobiology of suicidal behaviors.

Adolescent↗
PubMed1997

Beta-adrenoreceptor coupling to GS protein in alcohol dependence, panic disorder, and patients with both conditions.

Ethanol may downregulate G-protein-coupled beta-adrenoreceptors (beta AR). beta AR may also be dysregulated in panic disorder (PD). In clinical samples, many patients have comorbid alcohol dependence (AD) and PD. Therefore, we investigated beta AR coupling in patients with these disorders. We harvested polymorphonuclear leukocytes from 24 healthy volunteers (Vs), and from 22 abstinent AD patients, 7 PD patients, and 9 patients with comorbid AD/PD. beta AR were assayed using saturation and agonist-displacement experiments. Group differences were tested using one-way analysis of variance (ANOVA). All beta AR binding parameters were similar in AD patients and Vs. The ratio of the agonists' dissociation constant from the receptor in the low affinity state (KL) to that in the high affinity state (KH) was significantly higher in PD patients than in AD patients and Vs (930.97 +/- 440.80 vs. 226.2 +/- 94.47 vs. 197.05 +/- 61.03, respectively, p < .01). This finding suggests that beta AR are supercoupled to GS in patients with PD. There was a trend for higher total receptor density (RT) in AD/PD and PD patients (Vs = 39.06 +/- 42.57 vs. AD = 27.93 +/- 23.07 vs. AD/PD = 66.85 +/- 79.02 vs. PD = 68.36 +/- 49.20, p < .08). There were no differences between AD/PD and PD patients, who combined had a significantly higher RT than Vs and AD patients (Vs = 38.95 +/- 8.81 vs. AD = 29.63 +/- 5.07 vs. AD/PD = 67.51 +/- 17.00, fmol/mg protein, p < .04). Finally, AD/PD patients had a significantly higher receptor density in the low-affinity conformational state than Vs and AD patients, but not PD patients (25.96 +/- 11.59 vs. 10.69 +/- 1.53 vs. 7.62 +/- 1.08 vs. 17.07 +/- 5.26 fmol/mg protein, respectively, p < .005). beta AR function in polymorphonuclear leukocytes is normal in abstinent alcoholics. The previously reported abnormal beta AR regulation in alcoholism may be state dependent. The higher RT and KL/KH ratio in AD/PD and PD, but not in AD patients, suggest that increased beta AR function may be important in the pathophysiology of PD.

Adrenergic beta-Agonists↗
PubMed1997

Criminal and psychiatric histories of Finnish arsonists.

We investigated psychiatric and demographic variables and lifetime criminality among arsonists referred for a pre-trial psychiatric assessment. The medical and criminal records of 282 arsonists were studied in order to compare first-time and repeat offenders with regard to diagnostic, demographic and biological variables. Alcohol dependence and antisocial personality disorder were common among recidivist offenders. This finding was especially prominent among offenders who committed violent crimes. Recidivist offenders commonly had a history of long-lasting enuresis during their childhood. They were younger at the time of their first offence, and were more often intoxicated with alcohol during the arson attempt. Among arsonists, lifetime criminal recidivism was primarily associated with alcohol dependence and antisocial personality disorder. Psychosis was a common diagnosis among subjects who had no record of recidivist criminal offences.

Adult↗
PubMed1997

Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects.

OBJECTIVE: The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in healthy comparison subjects. METHOD: The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or type II alcoholics (early onset with antisocial traits) (N = 24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion. RESULTS: m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype. CONCLUSIONS: Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects.

Adrenocorticotropic Hormone↗
PubMed1997

Serum ionized magnesium in chronic alcoholism: is it really decreased?

Chronic alcoholism is associated with a marked deficit in total magnesium (tMg). However, little is known about the status of the physiologically active form, ionized magnesium (iMg). We assessed serum iMg (measured with two ion-selective electrodes, AVL 988-4 and NOVA CRT) and tMg concentrations in chronic alcoholics at admission (n = 31) and after abstinence (n = 13) and compared these results with those for a control group (n = 40). At admission, the tMg and NOVA iMg concentrations in alcoholics (0.78 +/- 0.020 and 0.38 +/- 0.016 mmol/L, respectively) were significantly less (P <0.001) than in the controls (0.85 +/- 0.008 and 0.50 +/- 0.006 mmol/L). The AVL iMg results, however, did not differ significantly between the two groups: 0.53 +/- 0.013 vs 0.56 +/- 0.006 mmol/L, respectively (P >0.05). The mean iMg between the two analyzers differed significantly in both groups (P <0.001). After 3 weeks of abstinence, the alcoholics showed a significant increase in tMg (P <0.001) and in both NOVA and AVL iMg values (P <0.01 for each). tMg concentrations were positively correlated with the AVL iMg values in both alcoholics and controls but correlated positively with the NOVA iMg results only in the controls. Thus, the altered status of iMg is instrument-dependent, and the usefulness of the measurement in alcoholics is yet to be determined.

Adult↗
PubMed1997

A nonhuman primate model of excessive alcohol intake. Personality and neurobiological parallels of type I- and type II-like alcoholism.

Developmental, biochemical, and behavioral concomitants of voluntary excessive alcohol consumption were investigated using a nonhuman primate model. Studies were designed to investigate potential neurobiological and behavioral parallels of Cloninger's subtypes of type I and type II alcoholism in nonhuman primates. The studies have shown that a subpopulation of primates chronically consume intoxicating amounts of alcohol. Subjects that chronically consume intoxicating amounts of alcohol often exhibit neurobiological and behavioral features that were predicted by Cloninger's model for subtypes of alcoholism among humans. Investigations showed that behavior patterns and biological indices that characterize high anxiety, whether constitutionally or stress induced, were correlated with high rates of alcohol consumption, consistent with predictions for type I alcoholism. Early untoward rearing experiences that increased anxiety increased the probability that subjects would chronically drink alcohol to intoxication. Investigations of type II-like alcohol consumption patterns focused on subjects with low central nervous system (CNS) serotonin functioning [as measured by reduced cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA)]. CSF 5-HIAA in infancy was shown to be a relatively stable neurobiological trait across development into adulthood. An individual CSF 5-HIAA concentration in infancy was shown to be a consequence of paternal and maternal genetic influences. Early parental neglect reduced CSF 5-HIAA concentrations. Low CSF 5-HIAA and CNS norepinephrine functioning were shown to predict excessive alcohol consumption in adolescence. Behaviorally, subjects with low CSF 5-HIAA demonstrated impaired impulse control, which resulted in excessive and inappropriate aggression, infrequent and inept social behaviors, low social status, social isolation and expulsion from social groups at an early age, and high rates of early mortality. With some exceptions, these findings were consistent with predictions from Cloninger's type II model of excessive alcohol consumption among men who exhibit impaired impulse control and violent and antisocial behaviors.

Alcoholic Intoxication↗
PubMed1996

CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors.

We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behaviour in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression. High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance.

Aggression↗
PubMed1996

Early-onset alcoholics have lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels than late-onset alcoholics.

BACKGROUND: We investigated the interrelationships of age at onset of excessive alcohol consumption, family history of alcoholism, psychiatric comorbidity, and cerebrospinal fluid monoamine metabolite concentrations in abstinent, treatment-seeking alcoholics. METHODS: We studied 131 recently abstinent alcoholics. Supervised abstinence was maintained on a research ward at the National Institutes of Health Clinical Center for a minimum of 3 weeks. All alcoholics received a low-monoamine diet for a minimum of 3 days before lumbar puncture. Lumbar punctures were performed in the morning after an overnight fast. Monamine metabolites and tryptophan in cerebrospinal fluid were quantified with liquid chromatography by means of electrochemical detection. Psychiatric diagnoses were established from blind-rated Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews administered by a research social worker. Severity and age at onset of excessive alcohol consumption were documented with a structured lifetime drinking history questionnaire and with selected alcoholism screening questionnaires (CAGE and Michigan Alcoholism Screening Test). Family history of alcoholism was obtained from the probands. RESULTS: A majority of the treatment-seeking, primarily white male alcoholics had a lifetime history of psychiatric disorders other than alcoholism. None fulfilled criteria for antisocial personality disorder. Early-onset alcoholics (onset of excessive consumption before 25 years of age) had a more severe course of alcoholism and lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid concentration than late-onset alcoholics. Patients who reported both parents to be alcoholics had particularly low mean cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan concentrations. CONCLUSION: Among treatment-seeking alcoholics, early age at onset is generally associated with a more severe course of alcoholism and lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.

Adult↗
PubMed1996

A prospective follow-up study of alcoholic violent offenders and fire setters.

BACKGROUND: This study investigated biochemical and family variables and predictors of recidivism among forensic psychiatric patients who had committed violent offenses or set fires. METHODS: One hundred fourteen male alcoholic violent offenders and fire setters were followed up for an average of 4.5 years after release from prison. At the beginning of their incarceration, the first half of the offenders were administered clinical diagnostic interviews, whereas the latter half received the Structured Clinical Interview for DSM-III (SCID) that was blind rated. A structured family history questionnaire was administered to all available first-degree relatives of offenders. The offenders also received lumbar punctures for monoamine metabolites, an oral glucose tolerance test, and a measurement of fasting plasma cholesterol level. At the end of the follow-up, the Finnish criminal registry was searched for recidivist crimes. RESULTS: Among all offenders, low cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations were associated with a family history positive for paternal alcoholism with violence. Low plasma cholesterol concentration was associated with a family history positive for paternal alcoholism without violence. The recidivists, who committed violent offenses or set fires during the follow-up period, had low CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations compared with those in nonrecidivists. Early family environments of the recidivists, compared with those of the nonrecidivists, were characterized by common paternal absence from and presence of brothers at home. CONCLUSION: Among male alcoholic violent offenders and fire setters, low CSF 5-HIAA and HVA concentrations are strongly associated with a family history positive for paternal violence and alcoholism, while low fasting plasma cholesterol concentration is associated with a family history positive for paternal alcoholism. Recidivist violent offenders and fire setters are predicted by low CSF 5-HIAA and MHPG concentrations and a developmental history positive for early paternal absence from and presence of brothers in the family of origin.

Adult↗