Multilocus Genetic Profile Reflecting Low Dopaminergic Signaling Is Directly Associated with Obesity and Cardiometabolic Disorders Due to Antipsychotic Treatment.

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.

Genetics of adult attachment: An updated review of the literature.

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.

Lithium: An old treatment for a new indication.

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’s level of autonomy increased. The possible relationship of this improvement to new data on the neuroprotective and neurotropic effects of lithium are discussed.

NOTA CLÍNICA: Litio: Un tratamiento antiguo para una nueva indicación / CLINICAL NOTE: Lithium: An Old Treatment for a New Indication a new indication

La encefalopatía necrotizante subaguda o síndrome deLeigh es una enfermedad neuro-metabólica congénita queforma parte de un grupo de enfermedades llamadas encefalopatías mitocondriales. Presenta una forma de herenciavariable y se produce una afectación multisistémica, aunquecon predominio de lesiones en el sistema nervioso central. Elpronóstico es malo y no existe un tratamiento específico. Enel año 2007, publicamos el caso de una paciente de 23 añosde edad con graves crisis de agitación psicomotriz, que tras elfracaso de varios tratamientos previos respondió favorablemente al litio1. Ahora describimos el seguimiento de esta paciente durante los 5 años posteriores tras el alta hospitalaria,hasta su fallecimiento a los 29 años. La mejoría se mantuvo,no volvió a ser hospitalizada y el nivel de autonomía de lapaciente aumentó. Se discuten las posibles relaciones de estamejoría con los nuevos datos sobre el efecto neuroprotectory neuroregenerador del litio. (AU)

Subacute necrotizing encephalopathy or Leigh’s syndrome is a congenital neuro-metabolic disease that is part ofa group of diseases called mitochondrial encephalopathies. Itpresents a variable form of inheritance and a multisystemicaffectation is produced, although with predominance of lesions in the central nervous system. The prognosis is poor andthere is no specific treatment. In 2007 we published the caseof a 23-year-old patient with severe psychomotor agitationcrises, who after the failure of several previous treatments,responded favorably to lithium1. We now describe the follow-up of this patient during the 5 years following her discharge from hospital, until her death at the age of 29. Theimprovement was maintained, she was not re-hospitalizedand the patient’s level of autonomy increased. The possiblerelationships of this improvement with the new data on theneuroprotective and neurotropic effects of lithium are discussed. (AU)

COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

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.

Aripiprazole reverses paliperidone-induced hyperprolactinemia.

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 paliperidoneinduced hyperprolactinemia within four weeks.

Aripiprazol como corrector de la hiperprolactinemia causada por paliperidona / Aripiprazole reverses Paliperidone-induced Hyperprolactinemia

La hiperprolactinemia es un efecto secundario frecuente provocado por los fármacos antipsicóticos. Una opción para resolver este problema es disminuir las dosis o cambiar de antipsicótico, pero en ocasiones se produce la descompensación del paciente. Comentamos el caso de una paciente en la que la combinación con 5 mg/día de aripiprazol resolvió en 4 semanas la hiperprolactinemia producida por la paliperidona (AU)

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 paliperidoneinduced hyperprolactinemia within four weeks (AU)