[Implications of chilean legal framework in teen pregnancy prevention: conflict and insecurity in health professionals]. / Implicancias del marco legal chileno en la prevención del embarazo adolescente: conflicto e inseguridad en los profesionales de la salud.

BACKGROUND: Teenage pregnancy is a psychosocial and multifactorial problem described as a lack of exercise of rights in sexual and reproductive health. There are important aspects in the doctor-patient relationship and confidentiality that directly affect the continuity and quality of care. There are controversies in the laws relating to the provision of contraception and confidentiality, and those that protect the sexual indemnity, especially in adolescents under 14 years. AIM: To describe the implications of the legal framework for professional midwives in the care of adolescents younger than 14 years in sexual and reproductive health. MATERIAL AND METHODS: In-depth interviews were conducted to 13 female and 2 male midwives working at Primary Health Care Centers in the Metropolitan Region. RESULTS: The attention of adolescents younger than 14 years in sexual and reproductive health involves medical-legal issues for health professionals. All professionals recognize that mandatory reporting sexual activity is a complex situation. All professionals notify pregnancies. In relation to the delivery of contraception, clinical care is problematic since professionals should take shelter from a legal standpoint. CONCLUSIONS: The medical-legal context of pregnant women under 14 years of age care generates a context of uncertainty and fear for professionals and becomes a source of conflict and insecurity in the exercise of the profession.

Limbic system mGluR5 availability in cocaine dependent subjects: a high-resolution PET [(11)C]ABP688 study.

Cocaine self-administration decreases type 5 metabotropic glutamate receptor (mGluR5) tissue concentrations in laboratory rats during early abstinence. These changes are thought to influence the drug's reinforcing properties and the ability of drug-related cues to induce relapse. Here, our goal was to measure brain regional mGluR5 availability in recently abstinent cocaine dependent humans. Participants meeting DSM-IV diagnostic criteria for current cocaine dependence (n=9) were recruited from the general population. mGluR5 availability (binding potential, non-displaceable; BPND) was measured with high-resolution positron emission tomography (PET HRRT) and [(11)C]ABP688. Compared to age- and sex-matched healthy controls (n=9), cocaine dependent subjects showed significantly lower BPND values in the ventral (bilateral: -28.2%, p=0.011), associative (right: -21.4%, p=0.043), and sensorimotor striatum (bilateral: -21.7%, p=0.045), amygdala (left: -26%, p=0.046) and insula (right: -23.3%, p=0.041). Among the cocaine users, receptor availabilities were related to abstinence (range: 2 to 14days). The longer the duration of abstinence, the lower the BPND values in the sensorimotor striatum (r=-0.71, p=0.034), left amygdala (r=-0.73, p=0.026) and right insula (r=-0.67, p=0.046). Compared to healthy controls, BPND values were significantly reduced in those who tested negative for cocaine on the PET test session in the ventral (p=0.018) and sensorimotor striatum (p=0.017), left amygdala (p=0.008), and right insula (p=0.029), but not in those who tested positive. Together, these results provide evidence of time-related mGluR5 alterations in striatal and limbic regions in humans during early cocaine abstinence.

Tryptophan hydroxylase(2) gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans.

Brain regional serotonin synthesis can be estimated in vivo using positron emission tomography (PET) and α-[((11))C]methyl-L-tryptophan ((11)C-AMT) trapping (K*) as a proxy. Recently, we reported evidence of lower normalized (11)C-AMT trapping in the orbitofrontal cortex (OBFC) of subjects meeting the criteria for an impulsive and/or aggressive behavioral phenotype. In this study, we examined whether part of the variance in OBFC serotonin synthesis is related to polymorphisms of the gene that encodes for the indoleamine's rate-limiting enzyme in the brain, tryptophan hydroxylase-2 (TPH(2)). In all, 46 healthy controls had PET (11)C-AMT scans and were genotyped for 11 single-nucleotide polymorphisms (SNPs) distributed across the TPH(2) gene and its 5' upstream region. Several TPH(2) SNPs were associated with lower normalized blood-to-brain clearance of (11)C-AMT in the OBFC. Dose-effect relationships were found for two variants (rs6582071 and rs4641527, respectively, located in the 5' upstream region and intron 1) that have previously been associated with suicide. Associations in the OBFC remained statistically significant in a mixed larger sample of patients and controls. These results suggest that in humans, genetic factors might partly account for variations in serotonin synthesis in the OBFC.

Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers.

Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean ± s.d. = 22.1 ± 3.4 years) [(11)C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg(-1), by mouth; n = 8) or placebo (3 × lactose, by mouth; n = 9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P ⩽ 0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P < 0.04), and voxel-based analyses showed larger stress-induced decreases in [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [(11)C]raclopride binding, primarily in the sensorimotor striatum (P < 0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked.

Increasing blood oxygen increases an index of 5-HT synthesis in human brain as measured using alpha-[(11)C]methyl-L-tryptophan and positron emission tomography.

The main objective of this investigation was to test the hypothesis that brain serotonin (5-HT) synthesis, as measured by trapping of alpha-[(11)C]methyl-L-tryptophan (alpha-MTrp) using positron emission tomography (PET), can be modulated by changes in blood oxygen. The study involved six healthy participants (three male and three female), who breathed a 15% or 60% oxygen mixture starting 15 min before the injection of tracer and continuing during the entire acquisition period. Participants were injected with up to 12m Ci of alpha-MTrp. Two sets of PET images were acquired while the participants were breathing each of the oxygen mixtures and, after reconstruction, all images were converted into brain functional images illustrating the brain trapping constant K(*) (microL/g/min). The K(*) values were obtained for 12 regions of interest outlined on the magnetic resonance images. The K(*) values obtained at high and low blood oxygen content were compared by paired statistics using Tukey's post hoc correction. As there were no difference in plasma tryptophan concentrations, these K(*) values are directly related to regional 5-HT synthesis. The results showed highly significant increases (50% on average) in brain serotonin synthesis (K(*) values) at high (mean value of 223+/-41 mmHg) relative to low (mean value 77.1+/-7.7 mmHg) blood oxygen levels. This suggests that tryptophan hydroxylase is not saturated with oxygen in the living human brain and that increases in blood oxygen can elevate brain serotonin synthesis.

Cardiovascular, neuroendocrine, and monoaminergic responses to psychological stressors: possible differences between remitted panic disorder patients and healthy controls.

Both clinical symptomatology and stress research suggest that panic attacks might be partially attributable to exaggerated psychophysiological responses to environmental stressors. In the present study, we aimed to explicitly test this idea by measuring the physiological responses to a mild psychological stressor in both healthy controls (n = 8) and fully remitted, medication-free panic disorder patients (n = 8). One hour before the stressor, former patients, compared to healthy controls, exhibited higher diastolic blood pressure. From a blood sample taken 30 min before the stressor, patients, compared to controls, had lower paroxetine platelet binding site densities. During the stressor, patients, compared to controls, had greater increases in plasma levels of cortisol. These preliminary findings suggest that remitted panic disorder patients might have disturbed physiological responses to mild psychological stressors. These disturbances might be related to the development of future episodes.

Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan.

We tested in normal human subjects a less invasive method to obtain plasma input function required in the calculation of the brain serotonin synthesis rate measured with positron emission tomography (PET) and alpha-[11C]methyl-tryptophan (alpha-MTrp). The synthesis rates derived with the arterial input function were compared to those derived from venous plasma and venous sinus time-radioactivity curves obtained from dynamic PET images. Dynamic PET images were obtained for the lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). Input functions were generated from both artery and vein in three subjects, and from artery only in two subjects. Net unidirectional uptake constants of alpha-MTrp (K*; mL/g/min) were calculated in several brain regions graphically using data between 20 and 60 minutes after injection with different input functions. In the five subjects with arterial sampling, we tested two methods for correcting the input functions from the venous samples: (1) normalization to the mean exposure time at 20 minutes from arterial curve; and (2) the use of the venous sinus curve for the first 20 minutes. Venous curves coincided with the arterial ones after about 20 minutes. When the venous curves were used, there was an underestimation of the area under the curves up to 20 minutes, resulting in a 5% to 30% overestimation of K* values. Combined use of the sinus curve up to 20 minutes and venous curve from 20 to 60 minutes as an input function resulted in the K* (mL/g/min) values larger by 7.1 +/- 3.8% than the K* values estimated with the arterial input function. Normalization of the venous curve to the exposure time at 20 minutes obtained from the arterial plasma curve resulted in a bias in the K* of about -0.34 +/- 3.32%. The bias from the K* values was propagated to the serotonin synthesis rates. The use of a combination of the venous blood samples and venous sinus as the input function resulted in an acceptable bias in the serotonin synthesis rates from the tissue time-radioactivity curves generated by PET.

Brain Regional alpha-[11C]methyl-L-tryptophan trapping in impulsive subjects with borderline personality disorder.

OBJECTIVE: Neurotransmission of serotonin (or 5-hydroxytryptamine [5-HT]) is thought to be disturbed in patients exhibiting impulsive behaviors. However, until recently it has not been possible to test this hypothesis in the brains of living humans. METHOD: Unidirectional trapping of the 5-HT precursor analog alpha-[(11)C]methyl-L-tryptophan (alpha-[(11)C]MTrp) has been proposed as an index of 5-HT synthesis capacity. The authors measured brain regional alpha-[(11)C]MTrp trapping with positron emission tomography in medication-free subjects with borderline personality disorder (N=13) and a healthy comparison group (N=11). Impulsivity was assessed by using a laboratory measure of behavioral disinhibition, go/no-go commission errors. RESULTS: Compared to healthy men, the men with borderline personality disorder had significantly lower alpha-[(11)C]MTrp trapping in corticostriatal sites, including the medial frontal gyrus, anterior cingulate gyrus, superior temporal gyrus, and corpus striatum. In the women with borderline personality disorder, significantly lower alpha-[(11)C]MTrp trapping was seen in fewer regions, but in both men and women, negative correlations with impulsivity scores were identified in the medial frontal gyrus, anterior cingulate gyrus, temporal gyrus, and striatum. CONCLUSIONS: Low 5-HT synthesis capacity in corticostriatal pathways may contribute to the development of impulsive behaviors in persons with borderline personality disorder.

Effects on mood of acute phenylalanine/tyrosine depletion in healthy women.

Catecholamines have been implicated in the etiology and pathophysiology of mood and anxiety disorders. In the present study, we investigated the effects of experimentally reducing catecholamine neurotransmission by means of acute phenylalanine/tyrosine depletion (APTD). Healthy female volunteers ingested: (1) a nutritionally balanced amino acid (AA) mixture (n = 14); (2) a mixture deficient in the serotonin precursor, tryptophan (n = 15); or (3) one deficient in the catecholamine precursors, phenylalanine and tyrosine (n = 12). Mood was measured at three times: at baseline and both immediately before and after an aversive psychological challenge (public speaking and mental arithmetic) conducted 5 hours after AA mixture ingestion. Acute tryptophan depletion (ATD) lowered mood and energy and increased irritability scores. These effects were statistically significant only after the psychological challenge. The effect of APTD on mood was similar to that of ATD. APTD did not attenuate the anxiety caused by the psychological challenge. These findings suggest that, in healthy women, reduced serotonin and/or catecholamine neurotransmission increases vulnerability to lowered mood, especially following exposure to aversive psychological events.

The effect of tryptophan depletion on mood in medication-free, former patients with major affective disorder.

Acute tryptophan depletion (ATD) induces transient clinical relapse in medicated patients with major affective disorder. Our objective was to determine whether this effect persists once patients are euthymic and off antidepressants. Thus, we examined the effects of ATD in fully remitted, medication-free, former patients with major depression (n = 14). ATD had no significant effect on mood. These results suggest that the previous report that ATD substantially lowers mood in pharmacologically treated patients reflects a reversal of mechanisms involved in the therapeutic effects of antidepressants. Alternatively, ATD might induce clinical relapse only in subgroups that have yet to be identified.

U-50,488H into A10 reduces haloperidol-induced elevations of accumbens dopamine.

Injections of kappa (k) opioid agonists into the A10 ventral tegmental area (VTA) induce behavioral inhibitions and decreased interest in incentive stimuli, behavioral changes indicative of decreased mesolimbic dopamine (DA) transmission. In seeming contrast, three separate laboratories have recently reported that intra-VTA injections of k agonists do not affect nucleus accumbens septi (NAS) basal levels of extracellular DA. In the present experiment, we investigated whether intra-VTA injections of a k agonist would decrease pharmacologically-stimulated increased levels of extracellular NAS DA. It was found that intra-VTA injections of the k agonist U-50,488H significantly attenuated haloperidol-induced elevations of DA, as measured by in vivo microdialysis.

The stimulation of central kappa opioid receptors decreases male sexual behavior and locomotor activity.

Systemic injections of the kappa (kappa) opioid receptor agonist U-50,488H decreased male sexual behavior, locomotor activity, body temperature and bodily grooming, and induced body flattening. The U-50,488H-induced inhibitions of male sexual behavior were prevented by systemic injections of naloxone and by intra-cranial injections of the kappa opioid antagonist nor-binaltorphimine (NBNI). Injections of NBNI to either the ventral tegmental area (VTA) or the nucleus accumbens septi (NAS) increased female-directed behavior, and prevented the U-50,488H-induced decreases in female-directed behavior. Intra-VTA NBNI prevented U-50,488H-induced decreases in the mean number of ejaculations, intra-NAS NBNI prevented U-50,488H-induced increases in copulation latencies. Intra-medial preoptic area (mPOA) injections of NBNI increased female-directed behavior, and attenuated U-50,488H-induced decreases in female-directed behavior as well as U-50,488H-induced increases in both copulation and ejaculation latencies. Injections of NBNI dorsal to the mPOA were ineffective. Two of 26 days following the central injection of NBNI, systemic injections of U-50,488H remained behaviorally ineffective, leaving both sexual behavior and locomotor activity undiminished. These results suggest that the stimulation of central kappa opioid receptors inhibits sexual behavior in the male rat; perhaps endogenous kappa opioid agonists induce sexual refractory periods.

Stress and depressed mood in medical students, law students, and graduate students at McGill University.

PURPOSE: To investigate stress in medical students, law students, and graduate students at McGill University using a well-validated measure, the Derogatis Stress Profile (DSP). METHOD: The DSP was administered to the medical students in November and December 1994. For comparison, the DSP was also administered to the undergraduate law students and the graduate students. In November 1995 the DSP was administered to the first- and second-year medical students. Results were analyzed with a number of statistical methods. RESULTS: The response rates for the medical students, the law students, and the graduate students in 1994-95 were 70%, 96%, and 43%, respectively. The response rate for the first- and second-year medical students in 1995-96 was 57%. The medical students had subjective feelings of stress that are marginally above population norms, but their total-stress scores (related to environmental factors, personality mediators, and emotional responses) were below those of the general population, the law students, and the graduate students. Elevated depression scores in a minority of the students did not seem to be related directly to the stresses associated with medical school. The transition from basic science training to clinical training was associated with an increase in stress and depressed mood. CONCLUSION: Medical students are not greatly stressed relative to other groups, hence other explanations must be sought for the elevated levels of depression in some students. One situation in which stress appears to be particularly important is in the transition from basic science training to clinical training. Targeted interventions may be an effective way of dealing with this problem.

Psychotic symptoms and vulnerability to recurrent major depression.

The demographic characteristics and psychiatric course of primary unipolar depressed patients, either with or without psychotic features, were compared in a retrospective study. 15% (25/165) of the patients had had at least one episode of psychotic depression. Compared with the 140 non-psychotic patients, the psychotic patients were more likely to be female, had been ill for significantly longer and endured significantly more episodes of depression. The greater number of episodes was not attributable to the greater length of illness. Various reasons for the group differences are examined. Particular consideration is given to the possibility that a propensity for recurrent psychotic major depression might be related to sensitized dopamine neurons.

Acute and repeated activation of male sexual behavior by tail pinch: opioid and dopaminergic mechanisms.

We studied the effect of tail pinch on male sexual behavior and its neurochemical basis. Male rats were gonadectomized and maintained on low doses of testosterone propionate (20.0 micrograms/day). Tail pinch significantly increased the percentage of males that mounted, intromitted, and ejaculated within a 30-min test, and these increases were attenuated by both pimozide (1.0 mg/kg, i.p.) and by naloxone (0.5, 1.0, and 2.0 mg/kg, s.c.). Moreover, tail pinch in the presence of an estrous female led to significantly increased female-directed behavior 48 h later during a test without tail pinch. Repeated tail pinch tests led to progressively more sexual activity, and the development of this behavioral sensitization was prevented by naloxone. These findings suggest that tail pinch increases the salience of the incentive characteristics of the female. Furthermore, during subsequent tests, with or without tail pinch, the increased salience of the female remains, as measured by the continued increases in sexual activity. These acute and sensitized behavioral increases might result from tail pinch-induced activation of the midbrain dopamine system via an opioid mechanism; either preventing tail pinch-induced dopamine activation (by an opioid antagonist) or blocking the effects of dopamine activation (by a dopamine antagonist) attenuated the long-term facilitation of sexual behavior seen after pairing the female with tail pinch.

Depressive relapse following acute tryptophan depletion in patients with major depressive disorder.

Acute tryptophan depletion (ATD) lowers serotonin synthesis and elicits depressive symptoms in some, though not all, remitted patients with major depressive disorder (MDD). In the present study, eight medication-free remitted patients with MDD, seasonal pattern, were tested twice, once following the ingestion of a tryptophan-containing mixture, once following ATD. ATD significantly increased Hamilton depression scores (p < 0.001). Four of the patients had a family history of psychiatric disorders: substance abuse (n = 4), mood disorders (n = 3) or Cluster B personality disorders (n = 3). The mood-lowering response to ATD was significantly greater in those patients with, than without, affected relatives (p < 0.001). These preliminary findings (1) support the hypothesis that depressed states are related to disturbed serotonin neurotransmission and (2) suggest that depressive symptoms following ATD might identify a subgroup of patients at high genetic risk for disorders associated with affective lability and dysregulated impulse-control, conditions thought to be related to low serotonin neurotransmission.

Preexposure to foot-shock sensitizes the locomotor response to subsequent systemic morphine and intra-nucleus accumbens amphetamine.

The effect of repeated exposure to foot-shock on locomotor activity was examined by testing rats in the shock boxes for one hour following shock exposure. Early in testing activity was elevated relative to the nonshocked control group, between 40-60 min following shock. Over days this period of elevated activity occurred sooner in time and lengthened in duration. When these animals were tested in the absence of shock, those preexposed to shock were more active following either saline or morphine (0.5 and 5.0 mg/kg IP) injections. In a second experiment, elevated spontaneous and morphine-induced activity was also found when rats had been preexposed to shock in boxes distinct from the activity test boxes. In a final experiment, animals preexposed to shock were tested after bilateral infusions of either amphetamine (5 and 10 micrograms/microliters/side) or morphine (5 micrograms/microliters/side) into the nucleus accumbens (NAS). On the amphetamine tests, previously shocked animals were significantly more active than control animals. In contrast, intra-NAS infusions of morphine failed to differentiate between the two groups. These results suggest that repeated mild foot-shock sensitizes the mesolimbic dopamine system by mechanisms similar to those mediating the sensitized behavioral and dopaminergic responses seen following repeated opioid or stimulant administration.

Pet studies of serotonin synthesis in the human brain.

The method for measuring serotonin synthesis in human brain uses [11C]alpha-methyl-L-tryptophan as a tracer and positron emission tomography. The alpha-methyl-L-tryptophan is converted to alpha-methylserotonin, which is not a substrate for monoamine oxidase and therefore accumulates in the brain. In a pilot study published recently, rates of serotonin synthesis were found to be higher in men than in women. This was due to the lower plasma free tryptophan in the women under the experimental conditions used, and does not necessarily reflect the situation in all circumstances. Acute tryptophan depletion lowered brain serotonin synthesis by 90% or more. Patients with borderline personality disorder, who exhibit emotional lability and impulsivity, may have lower brain serotonin synthesis rates than healthy controls.

A comparison of the effects of acute tryptophan depletion and acute phenylalanine/tyrosine depletion in healthy women.

Acute tryptophan depletion (ATD), which is thought to lower serotonin levels, can result in a lowering of mood. In the present study we compared the effect of ATD with acute phenylalanine/tyrosine depletion (APTD) in healthy women. Although considerable evidence relates catecholamines to the regulation of anxiety, there was no difference in anxiety responses in the ATD and APTD groups when the women underwent a mildly stressful psychological challenge. Both ATD and APTD caused a similar lowering of mood. Both depletions also increased heart rate. These results suggest that APTD is a useful method for studying the effect of low catecholamine levels in humans, and that catecholamines are involved in the regulation of mood.

Validación del cuestionario del modelo transteórico del cambio de ejercicio físico / Validation of the questionnaire of the transtheoretical model of change of physical exercice

El objetivo de este estudio fue traducir y validar al español el Cuestionario del Modelo Transteórico del Cambio de Ejercicio Físico de Prochaska y DiClemente (1983). Se utilizó una muestra de 812 personas, entre los 14 y los 88 años (29,5±21,7). Se realizó un análisis factorial confirmatorio, análisis de consistencia interna y validez predictiva. Los resultados del Cuestionario del Modelo Transteórico del Cambio de Ejercicio Físico presentaron valores adecuados (χ2/g.l = 4,3, CFI = 0,92, IFI = 0,92, TLI = 0,90, RMSEA = 0,06, SRMR = 0,05). La consistencia interna mostró valores encima de .70. Se halló una predicción positiva y significativa de los estadios más activos del Modelo Transteórico sobre la intención de ser físicamente activo. Este estudio ha permitido proporcionar un cuestionario válido y fiable para evaluar el estadio en el que se encuentran las personas con respecto a la práctica de ejercicio físico, en el ámbito español

The aim of this study was to translate and validate in Spanish the Questionnaire of the Transtheoretical Model of Change of Physical Exercise, of Prochaska and DiClemente (1983), and also to make adaptations and modifications as needed. The sample was composed of 812 people, aged between 14 and 88 years (29.5+21.7). Confirmative factorial analysis, analysis of internal consistency and of predictive validity were carried out. After the confirmative factorial analysis, the Questionnaire of the Theoretical Model of Change of Physical Exercise showed acceptable results (x2/g.1=4,3, CFI=0,92, IFI= 0.92, TLI = 0.90, RMSEA = 0.06, SRMR = 0,05). Similarly, internal consistency obtained from the respective dimensions showed values above .70. A positive and significant prediction of the most active stages of the Transtheoretical Model (action and maintenance) was found on the 'intention to be physically active'. This study has enabled the provision of a valid and reliable questionnaire