Hannu Naukkarinen

Reduced serotonin transporter binding in binge eating women

Abstract. Rationale: There is evidence that abnormalities in brain dopamine, norepinephrine and serotonin metabolism may play an important role in binge eating. Serotonin-active antidepressant drugs have also been found to decrease binge eating. Objective: We investigated serotonin transporter binding in obese binge-eating women. Eleven obese binge-eating and seven obese control women participated in the study. The subjects were not taking any medication known to affect serotonin (5-HT) transporters. Methods: We used single-photon emission tomography (SPECT) with the radioligand 123I-labelled nor-β-CIT, which specifically labels 5-HT transporters. Results: Obese binge-eating women showed significantly decreased 5-HT transporter binding in the mid-brain compared with obese controls (2.1±0.5 versus 2.9±0.5, respectively). Conclusions: SPECT imaging with a ligand specific for 5-HT transporters can be used to assess altered serotonin transporter binding in the living human brain. The results tentatively suggest that 5-HT transporter binding is decreased in binge-eating women.

Treatment improves serotonin transporter binding and reduces binge eating

RationaleSerotonin (5-HT) is involved in the control of eating behaviour by inhibiting food intake. Obese women with binge-eating disorder (OB-BED) were recently found to have reduced 5-HT transporter binding.ObjectivesThe aim of this study was to investigate the effect of a successful treatment on 5-HT transporters in OB-BED.MethodsThe 5-HT transporter binding of seven OB-BED was measured by single-photon emission computed tomography (SPECT), by using iodine-123-labelled nor-β-CIT as a tracer, before treatment and after successful treatment, when the OB-BED were asymptomatic. Treatment consisted of group psychotherapy and fluoxetine medication. The control subjects, six obese women without eating disorders, were also studied twice by using SPECT.ResultsThe 5-HT transporter binding of the symptomatically recovered OB-BED increased significantly (24±22%) after treatment, whereas in the control group, binding remained unchanged.ConclusionsThe results tentatively suggest that 5-HT transporter binding in OB-BED is an adaptive mechanism, which can be affected by treatment. Furthermore, there seems to be a link between improved 5-HT transporter binding and reduced binge eating.

Fluoxetine normalizes increased cardiac vagal tone in bulimia nervosa.

Patients with bulimia nervosa have been reported to respond to treatment with the serotonin uptake inhibitor fluoxetine. In a preliminary study, which had a small sample size, women with bulimia nervosa were reported to have elevated cardiac vagal tone. We investigated cardiac vagal tone in women with bulimia nervosa before and after treatment with fluoxetine. At baseline, resting cardiac vagal tone, deduced from the respiratory component of heart rate variability, was quantified in 41 healthy volunteer women and in 25 women with bulimia nervosa. The bulimic women received in a parallel-group design, double blind, either placebo or fluoxetine 60 mg/24 hr for 8 weeks. All patients participated in behavioral therapy. Resting cardiac vagal tone was measured again at the end of the treatment. Women with bulimia nervosa had higher cardiac vagal tone than age-matched healthy volunteer women. Placebo had no effect on cardiac vagal tone. Fluoxetine reduced cardiac vagal tone among the women with bulimia nervosa to a level similar to the healthy volunteer women. Women with bulimia nervosa have elevated resting cardiac vagal tone. Fluoxetine normalized the elevated resting cardiac vagal tone among the women with bulimia nervosa. At both the central and peripheral levels, vagal neurons are endowed with serotonin-3 receptors. In vitro, fluoxetine desensitizes or blocks serotonin-3 receptors. A controlled trial of serotonin-3 receptor blockers is warranted in bulimia nervosa.

Energy substrate metabolism among habitually violent alcoholic offenders having antisocial personality disorder

A large proportion of violent offences in Western countries are attributable to antisocial personality disorder (APD). Several studies have shown abnormal lipid, carbohydrate and low cerebrospinal fluid (CSF) monoamine metabolite levels in habitually violent alcoholic offenders with APD, but it is not clear how these biochemical abnormalities are related to each other in this disorder. We aimed to study energy substrate metabolism among habitually violent offenders with APD. Insulin sensitivity (euglycemic insulin clamp), basal energy expenditure (indirect calorimetry), and CSF 5-hydroxyindoleacetic acid (5-HIAA) measurements were performed on 96 habitually violent antisocial male alcoholic offenders and on 40 normal male controls. Habitually violent, incarcerated offenders with APD had significantly lower non-oxidative glucose metabolism, basal glucagon, and free fatty acids when compared with normal controls, but glucose oxidation and CSF 5-HIAA did not differ markedly between these groups. The effect sizes for lower non-oxidative glucose metabolism among incarcerated and non-incarcerated APD subjects were 0.73 and 0.51, respectively, when compared with controls, indicating that this finding was not explained by incarceration. Habitually violent offenders with APD have markedly lower glucagon and non-oxidative glucose metabolism when compared with healthy controls, and these findings were more strongly associated with habitual violent offending than low CSF 5-HIAA levels, a well-established marker for impulsive violent behavior. Follow-up studies are needed to confirm if abnormal glucose and lipid metabolism can be used to predict violent offending over the course of the APD offenders life span.

Long-term outcome after benzodiazepine withdrawal treatment in subjects with complicated dependence

BACKGROUND The study aimed to monitor subjects with benzodiazepine (BZ) dependence after withdrawal treatment in order to evaluate long-term outcome and predictors of remaining BZ-free. Subjects with high-dose dependence or co-occurring alcohol problems were not excluded. METHOD Seventy-six participants in an earlier, randomized, controlled trial of outpatient BZ discontinuation were interviewed, and documents from their treatment settings obtained, along with urine and serum samples for BZ use. Long-term outcomes for a cognitive-behavioral treatment group and a treatment-as-usual group were measured. RESULTS BZ discontinuation treatment outcomes were maintained in both treatment groups. No between-group differences were found. At the end of the study 25% of the subjects were BZ-free, and the median dose decrease from pre-treatment levels was 16.1 mg in diazepam equivalents. Subjects with pre-treatment doses exceeding 40 mg were able to maintain their doses at therapeutic levels through the follow-up. Pre-treatment low BZ dose, no previous withdrawal attempts, and high life satisfaction predicted success in staying BZ-free. CONCLUSIONS In subjects with complicated BZ dependence, the benefits of BZ discontinuation treatment may persist, but more studies are needed.

Urinary excretion of bufotenin (N,N-dimethyl-5-hydroxytryptamine) is increased in suspicious violent offenders: A confirmatory study

We previously reported that violent offenders with paranoid symptoms or whose violent actions had been directed against family members had higher urinary levels of bufotenin than other violent offenders. In the present study, patients were evaluated with the Karolinska Scales of Personality (KSP), and urinary levels of bufotenin were determined by mass spectrometry. In drug-free patients suspiciousness was positively correlated, and socialization was negatively correlated, with urinary bufotenin excretion. These two personality variables were strongly interdependent. In drug users, bufotenin excretion was correlated positively with social desirability and negatively with irritability, but not with suspiciousness. Bufotenin excretion was not found to be associated with violence toward family members in the present study. The results are in keeping with the earlier finding that violent offenders with paranoid personality traits have higher urinary levels of bufotenin than other violent offenders.

Urinary excretion of free bufotenin by psychiatric patients

According to the methylation hypothesis of mental disorders, the human body is capable of producing toxic methylated substances that play a part in the patbogenesis and symptomatology of psychiatric disease. Earlier attempts to show that the methylated indoleamines bufotenin (N,Ndimethylserotonin) and DMT (N.N-dimethyltryptamine) are present in increased quantities in schizophrenia (Wyatt et al. 1971) were largely hampered by difficulties in analytical methodology. These indoleamines can now be determined reliably by gas chromatography-mass spectrometry (GC-MS) (Walker et al. 1973; Riiisanen and K&&k&en 1979). Using GC-MS, we have shown that bufotenin is also excreted into urine in healthy humans as a free form and as a conjugate (R%istien and K&rkkainen 1979; Rg;isanen 1984). Comparable levels have also been found by liquid chromatography (Riceberg and Van Vunakis 1978; Sitaram et al. 1983).

Plasma endogenous opioids and dexamethasone suppression test in depression

Plasma levels of beta-endorphin plus beta-lipotropin were determined in 35 hospital patients with depression and in 23 controls before and after administration of 1 mg of dexamethasone (dxm). Dxm suppressed opioid secretion in both groups. The opioid levels of the patients were significantly higher than those of the controls both before and after dxm. All the controls were cortisol suppressors. Among the patients the post-dxm opioid levels of cortisol nonsuppressors (n = 14) were higher than those of cortisol suppressors (n = 21). A significant correlation between the opioid and cortisol levels was found in the patients. There was a significant association between the use of neuroleptics and high opioid levels, but the difference between the patients and the controls was not explained by the effect of any single class of drugs. The results support the concept of hypersecretion of corticotropin-releasing factor in depression.

Predictors of Benzodiazepine Discontinuation in Subjects Manifesting Complicated Dependence

We described characteristics of subjects with benzodiazepine dependence that was typically complicated by harmful and hazardous alcohol use or high benzodiazepine doses, and assessed predictors of successful discontinuation of benzodiazepines for this group. Seventy-six patients who participated in a randomized clinical trial of two different gradual withdrawal treatment approaches were assessed. The trial was conducted between February 1995 and July 1999. The mean age ±SD of subjects was 40.0±9.6 years, 55% were male, 38% were married or cohabiting, and 70% had received more than nine years of education. The median benzodiazepine dose was 35 mg /day (range 2.5–180) in diazepam equivalents. The median duration of benzodiazepine use was 84 (range 8–360) months. Subjects with lower benzodiazepine doses and no previous withdrawal attempts were more successful at benzodiazepine discontinuation. Cluster B personality/borderline personality disorder was associated with an inability to stop benzodiazepine use and with “dropping out” of treatment. Alcohol use–related disorders or other psychiatric diagnoses were not associated with outcome. Further studies on predictors of successful benzodiazepine discontinuation in different populations are required. Patients manifesting cluster B personality/borderline personality disorder and benzodiazepine dependence may need concomitant treatment for their personality disorders to benefit from benzodiazepine discontinuation treatment.

Interf eron-α as Adjuvant Treatment in Chronic Schizophrenia

The therapeutic use of interferon (IFN)-α administered as adjuvant medication in chronic schizophrenia was investigated. Natural leukocyte IFN-α was given to 9 long-term hospitalized chronic schizophr