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Treatment with second-generation antipsychotics (SGAs) can cause obesity and other cardiometabolic disorders linked to D2 receptor (DRD2) and to genotypes affecting dopaminergic (DA) activity, within reward circuits. We explored the relationship of cardiometabolic alterations with single genetic polymorphisms DRD2 rs1799732 (NG_008841.1:g.4750dup -> C), DRD2 rs6277 (NG_008841.1:g.67543C>T), COMT rs4680 (NG_011526.1:g.27009G>A), and VNTR in both DRD4 NC_000011.10 (637269-640706) and DAT1 NC_000005.10 (1392794-1445440), as well as with a multilocus genetic profile score (MLGP). A total of 285 psychiatric patients treated with SGAs for at least three months were selected. Cardiometabolic parameters were classified according to ATP-III and WHO criteria. Blood samples were taken for routinely biochemical assays and PCR genotyping. Obesity (BMI, waist (W)), high diastolic blood pressure (DBP), and hypertriglyceridemia (HTG) were present in those genetic variants related to low dopaminergic activity: InsIns genotype in rs1799732 (BMI: OR: 2.91 [1.42–5.94]), DRD4-VNTR-L allele (W: OR: 1.73 [1.04–2.87]) and 9R9R variant in DAT1-VNTR (W: OR: 2.73 [1.16–6.40]; high DBP: OR: 3.33 [1.54–7.31]; HTG: OR: 4.38 [1.85–10.36]). A low MLGP score indicated a higher risk of suffering cardiometabolic disorders (BMI: OR: 1.23 [1.05–1.45]; W: OR: 1.18 [1.03–1.34]; high DBP: OR: 1.22 [1.06–1.41]; HTG: OR: 1.20 [1.04–1.39]). The MLGP score was more sensitive for detecting the risk of suffering these alterations. Low dopaminergic system function would contribute to increased obesity, BDP, and HTG following long-term SGA treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Arrue A, Gómez FM, Giralt MT. Effects of 3,4-methylenedioxymethamphetamine (‘Ecstasy’) on the jaw-opening reflex and on the α 2 -adrenoceptors which regulate this reflex in the anesthetized rat. Eur J Oral Sci 2004; 112: 127–133. © Eur J Oral Sci, 2004 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 α2-adrenoceptors which, in an inhibitory way, regulate it. Increasing doses of MDMA (1–29440 µg kg−1) induced an incomplete inhibition of JOR and 50% inhibition (ED50) at 2550 µg kg−1; maximal inhibition was 88%. The repeated treatment with MDMA led to an enhancement of the inhibition of JOR induced by the α2-agonist, clonidine (ED50 was reduced by 77%), indicating an increased sensitivity of the α2-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. [ABSTRACT FROM AUTHOR]

Examines the effect of stress on striatal dopamine metabolism by the expression of non-functional masticatory activity in rats. Inducement of central noradrenergic neurotransmission through stress; Involvement of striatal dopaminergic neurotransmission in oral movements in rats; Application of tail pinch as stressor.

Hyperprolactinemia is a common side effect of antipsychotic treatments. Existing alternatives to resolve this problem include decreasing the antipsychotic dose or switching to a different antipsychotic agent. Nevertheless, said modifications can lead to other adverse consequences, such as the worsening of psychotic symptoms. We report a clinical case in which an adjunctive treatment with aripiprazole (5 mg/day) reversed paliperidone-induced hyperprolactinemia within four weeks. [ABSTRACT FROM AUTHOR]

Hyperprolactinemia is a common side effect of antipsychotic treatments. Existing alternatives to resolve this problem include decreasing the antipsychotic dose or switching to a different antipsychotic agent. Nevertheless, said modifications can sometimes lead to decompensation of the patient. We report a clinical case of a female patient in whom the combined treatment of 5 mg/day of aripiprazole (5 mg/day) reversed paliperidone-induced hyperprolactinemia within four weeks. [ABSTRACT FROM AUTHOR]

Depression is a common, recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide. Up to 15%-40% of cases do not respond to diverse pharmacological treatments and, thus, can be defined as treatment-resistant depression (TRD). The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment. Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD. Specifically, the N-methyl-D-aspartic acid receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), which are targeted by ketamine and esketamine, are proposed as promising pathways. A literature search was performed to identify studies on the genetics of the glutamatergic system in depression, focused on variables related to NMDARs and AMPARs. Our review highlights GRIN2B , which encodes the NR2B subunit of NMDAR, as a candidate gene in the pathogenesis of TRD. In addition, several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation. These genes encoding glutamatergic receptors could, therefore, be candidate genes for understanding the etiopathogenesis of TRD, as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)