Search

Attachment style, which has been theorized to be rooted in childhood bonding experiences, influences adult cognitive, emotional and interpersonal functioning. Despite its relationship with early experiences, research indicates that the continuity of attachment style across childhood and adulthood is only partial, being a malleable tendency that is shaped throughout development, with an increasing influence of genetics, as it occurs in other cognitive and behavioral phenotypes. Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes, but the precise mechanisms remain unclear. A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin, dopaminergic pathways, serotonergic pathways and brain-derived neurotrophic factor in adult attachment, with both vulnerability and differential susceptibility approaches, yielding mixed results. We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation. Based on the existing data, we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.

Insecure attachment has been described as mediating the relationship between childhood trauma and dysfunctional personality traits in different mental disorders. Despite the role insecure attachment and childhood trauma have independently demonstrated to play as determinants of borderline personality disorder, less is known about the mediating mechanisms explaining these associations. For the first time, we assessed adult attachment, childhood trauma and dimensional personality pathology in a sample of outpatients with borderline personality disorder and tested whether the association between childhood trauma and personality dysfunction was at least partially attributable to insecure attachment. The results showed that attachment anxiety fully mediated the relationship between specific types of trauma (emotional abuse and physical neglect) and emotional dysregulation. Further, emotional abuse was both directly associated with dissocial behaviour and indirectly via attachment anxiety (partial mediation). Emotional abuse has been described as an essential environmental factor for the development of borderline personality disorder and emotional dysregulation, on its part, as the core feature of the condition. Our results indicate that attachment anxiety explains the link between these central aspects of borderline personality disorder. Our findings are consistent with previous research and current etiological understanding of the condition and provide support for recommending a careful assessment of childhood traumatic experiences and adult attachment style to gain a more comprehensive insight into the symptoms and its heterogeneity. As a secondary aim, we assessed the effect parental mental illness may have in these mediation models, but no significant influence on childhood trauma, attachment or personality was found. This work was supported by the Health Department of the Basque Government under grant PI2014111034, by Biocruces Bizkaia Health Research Institute and by the Research Unit of Galdakao-Usansolo Hospital. Open access funding was provided by the University of the Basque Country UPV/EHU.

Subacute necrotising encephalopathy or Leigh syndrome is a congenital neuro-metabolic disease that is part of a group of diseases called mitochondrial encephalopathies. The form inherited is variable and it has a multisystemic effect, although with a predominance of lesions in the central nervous system. Prognosis is poor and there is no specific treatment for it. In 2007, we published the case of a 23-year- old patient, with severe psychomotor agitation crises, who responded favourably to lithium1 after the failure of several previous treatments. Here, we describe the follow-up of this patient during the 5 years after discharge from hospital, until her death at 29 years of age. Her improvement was maintained, she was not hospitalised again and the patient#8217;s level of autonomy increased. The possible relationship of this improvement to new data on the neuroprotective and neurotropic effects of lithium are discussed.

Facial emotion recognition (FER) has been described to be impaired in borderline personality disorder (BPD), especially for neutral faces. Genetic modulation of FER has been studied in healthy individuals and some psychiatric conditions, but no genetic association studies have been conducted in BPD hitherto. The main objective of our study was to explore the influence of the serotonin-transporter-linked promoter region (5HTTLPR) and catechol-o-methyltransferase (COMT) Val158Met on facial emotion processing among BPD patients. To that end, seventy-six BPD outpatients were asked to complete a computer-based facial affect recognition task, representing four emotions (neutral, happy, fearful or angry). Accuracy of FER and perceptual biases were calculated. The 5HTTLPR and COMT Val158Met polymorphisms were genotyped using saliva samples. Individuals with the high-activity serotonin-transporter genotype and those with the low-activity COMT genotype had significantly more difficulties identifying neutral faces; the former showed stronger bias to perceive neutral faces as happy, and the latter, neutral faces as fearful. Interestingly, the perceptual biases observed in our patients are similar to previous reports in healthy individuals. The authors propose that the ability to accurately recognize neutral faces might be a possible endophenotype of BPD. Sex-genotype interactions were also observed in relation to angry faces and 5HTTLPR, and neutral faces and COMT Val158Met polymorphisms, in line with sex-related differences previously described for both polymorphisms in relation to FER and other cognitive and behavioral outcomes. The impact of inaccurate FER on psychosocial functioning and potential interventions are also discussed.

Dysfunctional noradrenergic transmission is related to several neuropsychiatric conditions, such as depression. Nowadays, the role of G protein-coupled inwardly rectifying potassium (GIRK)2 subunit containing GIRK channels controlling neuronal intrinsic excitability in vitro is well known. The aim of this study was to investigate the impact of GIRK2 subunit mutation on the central noradrenergic transmission in vivo. For that purpose, single-unit extracellular activity of locus coeruleus (LC) noradrenergic neurons and brain monoamine levels using the HPLC technique were measured in wild-type and GIRK2 mutant mice. Girk2 gene mutation induced significant differences among genotypes regarding burst activity of LC neurons. In fact, the proportion of neurons displaying burst firing was increased in GIRK2 heterozygous mice as compared to that recorded from wild-type mice. Furthermore, this augmentation was even greater in the homozygous genotype. However, neither the basal firing rate nor the coefficient of variation of LC neurons was different among genotypes. Noradrenaline and serotonin basal levels were altered in the dorsal raphe nucleus from GIRK2 heterozygous and homozygous mice, respectively. Furthermore, noradrenaline levels were increased in LC projecting areas such as the hippocampus and amygdale from homozygous mice, although not in the prefrontal cortex. Finally, potency of clonidine and morphine inhibiting LC activity was reduced in GIRK2 mutant mice, although the efficacy remained unchanged. Altogether, the present study supports the role of GIRK2 subunit-containing GIRK channels on the maintenance of tonic noradrenergic activity in vivo. Electric and neurochemical consequences derived from an altered GIRK2-dependent signalling could facilitate the understanding of the neurobiological basis of pathologies related to a dysfunctional monoaminergic transmission.

Aim: We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. Patients & methods: We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. Results: Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. Conclusion: Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.

Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

It has been suggested that the family history of psychotic disorders is useful in defining homogeneous groups of bipolar patients. The plasma homovanillic acid (pHVA) concentrations have been related to the effect of antipsychotic treatment in psychotic patients. We have studied the influence of a positive family history of psychotic disorders both on the variation of pHVA levels and on the relation between pHVA concentrations and the clinical response to treatment. Clinical status and pHVA levels were assessed in 58 medication free patients before and after 4 weeks of treatment with olanzapine and lithium. Clinical improvement correlated positively with pHVA levels on the 28th day of treatment only in the patients having first degree relatives with psychotic disorders. The pHVA levels did not decrease after 28 days of treatment. Our results reinforce the idea that a positive family history of psychosis in psychotic bipolar disorders may constitute a good basis for sub-grouping these patients.

El diagnostico del paciente en el que coexisten sintomas afectivos y sintomas psicoticos entrana cierta dificultad. En primer lugar tenemos que ver si el paciente tiene un trastorno afectivo, y en Segundo lugar, si presenta sintomatologia psicotica, tenemos que decidir si esta es congruente o no con el estado de animo. En este articulo se revisa la situacion actual de este tema, y se contrastan las opiniones de distintos autores. Tambien se reflexiona sobre los puntos donde mas dificultades encontramos a la hora de diagnosticar a estos pacientes, como que presente delirios persecutorios o sintomas de primer rango de Schneider. Se concluye que son necesarias bases mas objetivas para clasificar a estos pacientes.

Several findings suggest that glial cell line-derived neurotrophic factor (GDNF) may be a useful tool to treat parkinsonism by acting as a neuroprotective and neurotrophic factor for dopaminergic neurotransmission systems. In the present study, we implanted alginate-poly-L-lysine-alginate microcapsules containing immobilized Fischer rat 3T3 fibroblasts transfected to produce GDNF in vitro into the striatum of 6-hydroxydopamine (6-OHDA) lesioned rats. Microencapsulated GDNF secreting cells were stable for at least 3 weeks in vitro. Intrastriatal implantation of microencapsulated GDNF secreting cells into 6-OHDA lesioned rats resulted in a decrease in apomorphine-induced rotations by 84%, 64%, 84%, 60% and 52% (2, 5, 8, 16 and 24 weeks, respectively) with respect to the value before implantation and with respect to the value obtained from the empty microcapsule implanted-group at each time point. Six months after transplantation, immunohistochemical detection of GDNF revealed strong immunoreactivity in the striatal tissue surrounding the microcapsules in the absence of tissue damage due to microcapsule implantation. No changes in the levels of dopamine and its metabolites or of tyrosine hydroxylase immunoreactivity were detected in the striatum. In summary, the implantation of microencapsulated GDNF secreting cells allows the delivery of this molecule into the rat striatum for at least 6 months and results in substantial behavioral improvement.

The relation between changes in the levels of plasma homovanillic acid (pHVA) and clinical evolution during neuroleptic treatment of schizophrenic patients has not been satisfactorily characterized, as a number of conflicting findings have been reported. Significant correlations have generally been found using the assessment of positive symptoms as an index of clinical outcome. Nevertheless, attempts to correlate pHVA concentrations with negative symptoms have yielded contradictory results. With a view to evaluating if different responses in negative symptoms are associated with distinct pHVA profiles, we examined the levels of pHVA in 46 neuroleptic-free schizophrenic patients and in these patients after neuroleptic treatment. Negative and positive symptoms were also addressed before and after treatment. Our results reveal that at least two classes of negative symptoms exist; the clinical evolution of the first class of negative symptoms parallels that of positive symptoms, and clinical improvement correlates with reduced dopaminergic activity. In contrast, in the second class, reduced dopaminergic activity is associated with a further deterioration of negative symptoms. These findings corroborate the heterogeneity of negative symptoms and may contribute to a better definition of endophenotypes in the schizophrenic syndrome.

Introduccion Los estudios mas recientes apoyan la idea de que la fisiopatologia del sindrome bipolar se sustenta en diversas interacciones de varios sistemas de neurotransmision. Datos clinicos y preclinicos sugieren tambien que la actividad noradrenergica esta elevada en estos pacientes antes del tratamiento. Metodo En nuestro estudio se ha medido la concentracion plasmatica del 3-metoxi-4-hidroxifenilglicol (MHPG), principal metabolito de la noradrenalina (NA), en 50 pacientes bipolares tipo I, 29 varones y 21 mujeres, diagnosticados segun el Diagnostic and Statistical Manual of Disorders (DSM-IV). Tambien se determinaron los polimorfismos Val108/158Met de la catecol-O-metiltransferasa (COMT). Los pacientes se trataron con olanzapina, a la que posteriormente se anadio litio. Resultados y Conclusiones El tratamiento demostro ser eficaz, tanto en pacientes psicoticos como en no psicoticos; y no se encontro una relacion significativa entre los polimorfismos estudiados de la COMT y la respuesta clinica medida por la escala de Young para la mania. Si se puso de manifiesto una correlacion significativa y positiva entre los valores plasmaticos de MHPG antes del tratamiento y despues de 3 dias de tratamiento con la respuesta a este.

Background The activity of catechol-O-methyltransferase (COMT) may be related to psychosis susceptibility. The Val108/158Met polymorphism of the COMT gene influences its enzymatic activity and may result in altered concentrations of monoamine metabolites and different clinical responses of patients to pharmacological treatments. Methods We examined in a sample of 42 bipolar patients if the Val108/158Met polymorphism influences: (a) the presence of psychosis in type I bipolar patients; (b) the blood plasma concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), which are metabolites of dopamine and noradrenaline respectively and (c) the severity of the clinical characteristics of these patients and their response to pharmacological treatment. Results No significant associations were found between the studied COMT genotypes and the studied parameters. However, a non-significant aggregation of bipolar patients presenting with psychosis was found in the homozygous Val-Val group. Clinical improvement was found to significantly correlate with the levels of plasma MHPG prior to treatment. Moreover, a significant difference was found between the standard deviations of the concentrations of HVA in the three genotypes, but not in their mean values. Significant associations were not detected between COMT polymorphisms and the initial severity of the disorder, or the clinical response to pharmacological treatment. Limitations The size of the studied sample is somewhat small and comparisons have been made with a previously studied control group. Conclusions The Val108/158Met polymorphism does not appear to be a crucial determinant in type I bipolar disorder.

Bruxism, principally jaw clenching, is frequently observed in users of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA). It has been suggested that during bruxism a reduction of the activity of oral protective reflexes occurs. In this study we investigated the effects of intravenously administered MDMA on the digastric electromyographic responses elicited by orofacial electrical stimulation in the rat. We also assessed the effects of either the administration of a single dose (20 mg kg(-1), s.c.) or repeated doses of MDMA (same dose, twice a day, for 4 d) on the jaw-opening reflex (JOR) and on the sensitivity of the alpha(2)-adrenoceptors which, in an inhibitory way, regulate it. Increasing doses of MDMA (1-29440 micro g kg(-1)) induced an incomplete inhibition of JOR and 50% inhibition (ED(50)) at 2550 micro g kg(-1); maximal inhibition was 88%. The repeated treatment with MDMA led to an enhancement of the inhibition of JOR induced by the alpha(2)-agonist, clonidine (ED(50) was reduced by 77%), indicating an increased sensitivity of the alpha(2)-adrenoceptors. This study shows that the intravenous administration of MDMA reduces the JOR while repeated doses of the drug enhance the inhibitory noradrenergic mechanisms which regulate the reflex. The results also allow speculation that a reduction of JOR may underlie the occurrence of episodes of bruxism in MDMA users.

This study was undertaken to investigate the effects of the administration of 3,4-methylenedioxymethamphetamine (MDMA) on the locus coeruleus firing rate, on the sensitivity of the alpha(2)-adrenoceptors which regulate neuronal activity and on the in vivo tyrosine hydroxylase activity in hippocampus. The basal firing rate was not modified by either a single dose or repeated doses of MDMA, although the latter produced a shift to the right in the dose-response curve for clonidine-induced inhibition of the firing rate (ED(50) increased by 59%) and a reduction in tyrosine hydroxylase activity (20%) in the hippocampus. However, 8 days after the final dose alpha(2)-adrenoceptor sensitivity and tyrosine hydroxylase activity had returned to control values. Our results show a desensitization of alpha(2)-adrenoceptors in locus coeruleus and the existence of short-term changes in the noradrenergic system.

El trastorno bipolar es una enfermedad cronica, caracterizada por remisiones y exacerbaciones, cuya evolucion puede modificarse favorablemente con un tratamiento apropiado. Aunque el tratamiento de los episodios agudos es importante, la prevencion de recaidas mediante un tratamiento de mantenimiento es el objetivo terapeutico principal. Se ha estimado que aproximadamente el 60% de la poblacion diagnosticada de trastorno bipolar I experimenta de forma cronica dificultades en la actividad sociolaboral. Los sintomas subclinicos entre los episodios agudos son, en un gran numero de pacientes, la causa de esas dificultades. Presentamos el caso de una paciente con subsintomas interepisodicos, a la que instauramos un tratamiento con aripiprazol. Este neuroleptico, de singular mecanismo de accion, ha producido en nuestra paciente sorprendentes consecuencias clinicas de interesante discussion.

It is thought that the expression of oral parafunctions may provide an outlet for stress or aggressiveness in man. Stress-induced increases in central noradrenergic neurotransmission are attenuated in rats which are allowed to bite during stress. Striatal dopaminergic neurotransmission is involved in the genesis of parafunctional oral movements in rodents. As tail pinch is the stressor which most clearly provokes non-functional masticatory activity (NFMA), and also increases striatal dopamine (DA) activity in rats, we investigated whether the expression of NFMA during tail pinch could modify the changes in striatal dopaminergic neurotransmission induced by this stressor. Rats were subjected to tail pinch for 5 min, and the duration of the NFMA displayed was recorded. As an index of dopaminergic activity, 3,4-dihydroxyphenylalanine (DOPA) accumulation and DA and 3,4-dihydroxyphenylacetic (DOPAC) contents in both striata were determined by high-performance liquid chromatography. Striatal DOPA accumulation was similarly increased in relation to control, both in rats which did and did not display NFMA during tail pinch. However, the increases in striatal DOPAC contents, reported 24 min after the stress session, were lower in animals which had displayed NFMA. These results provide further evidence in support of the assumption that the expression of parafunctional masticatory activity attenuates the effects of stress on central catecholaminergic neurotransmission.

In the present study we have measured, on a monthly basis, the concentration of plasma homovanillic acid (pHVA) in schizophrenic patients during 13 months of their pharmacological treatment. The average pHVA values of each patient were within the range of 7.30–17.70 ng/ml and the coefficients of variation for each patient (CV %) were within the range of 13–33%. Half of the patients that showed higher pHVA CV% values also showed higher scores on the Brief Psychiatric Rating Scale at the beginning of the study, and improved more after 6 months, when compared to the remaining 50% with lower CV% values. There was no significant relationship between the scores of the Wisconsin Card Sort Test and the concentration or the CV% of the pHVA of each patient. A greater variability in the pHVA may be associated with a greater plasticity of the dopaminergic system and a better clinical response.

We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research.

We examined the catechol-O-methyl transferase (COMT) Val108/158Met genotype in 160 type 1 bipolar patients. We also analyzed the plasma concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG) and 3,4-dihydroxyphenylacetic acid in 60 of those patients who had been without mood stabilizers or neuroleptic treatment for at least 8 days. Results: Patients with congruent psychotic symptoms presented a higher plasma concentration of HVA than mood incongruent psychotic patients. The Val/Val genotype was associated with higher plasma concentrations of HVA and MHPG. We detected a larger proportion of patients with psychotic symptoms in the Val/Val genotype group, although this did not reach statistical significance. It was found that the distribution of the COMT genotype was not influenced by the congruent/incongruent nature of the psychotic symptoms. Limitations: The proportion of patients without psychotic symptoms in our sample was low. This fact limits the value of some comparisons. Conclusions: Congruent and incongruent psychotic patients can be distinguished in terms of the concentration of plasma HVA. Based on the presence or absence of mood incongruent symptoms, the Val108/158Met polymorphism of the COMT gene alone does not appear to be a crucial determinant in the division of psychotic bipolar patients. Nevertheless, COMT polymorphisms may influence some of the characteristics of the patients by their effect on monoamine metabolism.

BACKGROUND Changes in the levels of homovanillic acid in blood plasma (pHVA) may reflect changes which occur in the brain. In healthy individuals, this concentration of pHVA is stable over time. METHODS Over the course of one month, we studied 98 acute schizophrenic patients who had not been taking any medication but were administered neuroleptics upon hospital admission, together with 23 chronic schizophrenic patients on long-term treatment from whom medication was withdrawn. Blood samples were taken at regular intervals from each individual and the concentration of plasma homovanillic acid was measured. RESULTS We found relative stable values of pHVA with an intraclass correlation coefficient of 0.363 in acute patients and 0.638 (p

6 p. Introduction: Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger's Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3 +/- 12.5 vs. 55.3 +/- 8.1) and self-transcendence (45.3 +/- 12.8 vs. 32.7 +/- 8.2) and scored lower than controls in self-directedness (68.8 +/- 13.3 vs. 79.3 +/- 8.1), cooperativeness (77.1 +/- 9.1 vs. 83.9 +/- 6.5) and persistence (60.4 +/- 15.1 vs. 67.1 +/- 8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val.-- Conclusions: Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain's reward circuits. Supported in part by grant 2008111051 of the Basque Government’s Department of Health and by Grant PS0901760 of the Fondo de Investigación Sanitaria and FEDER Funds, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.