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.

Prolactin and morning cortisol concentrations in antipsychotic naïve first episode psychosis: A systematic review and meta-analysis.

IMPORTANCE: Alterations in prolactin and cortisol levels have been reported in antipsychotic naïve patients with first episode psychosis (FEP). However, it has been studied in very small samples, and inter-group variability has never been studied before. OBJECTIVE: To provide estimates of standardized mean differences (SMD) and inter-group variability for prolactin, cortisol awakening response (CAR) and morning cortisol concentrations in antipsychotic naïve FEP (AN-FEP) patients and healthy controls (HC). DATA SOURCES: BIOSIS, KCI, MEDLINE, Russian Science Citation Index, SciELO, Cochrane, PsycINFO, Web of Science were searched from inception to February 28, 2022. STUDY SELECTION: Peer-reviewed cohort studies that reported on prolactin or cortisol blood concentrations in AN- FEP patients and HC were included. DATA EXTRACTION AND SYNTHESIS: Study characteristics, means and standard deviations (SD) were extracted from each article. Inter group differences in magnitude of effect were estimated using Hedges g. Inter-group variability was estimated with the coefficient of variation ratio (CVR). In both cases estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression. PRISMA guideline was followed (No. CRD42022303555). MAIN OUTCOMES AND MEASURES: Prolactin, CAR and morning cortisol blood concentrations in AN-FEP group in relation to HC group. RESULTS: Fourteen studies for prolactin (N = 761 for AN-FEP group, N = 687 for HC group) and twelve studies for morning cortisol (N = 434 for AN-FEP group, N = 528 for HC group) were included. No studies were found in CAR in AN-FEP patients. Mean SMD for prolactin blood concentration was 0.88 (95% CI 0.57, 1.20) for male and 0.56 (95% CI 0.26, 0.87) for female. As a group, AN-FEP presented greater inter-group variability for prolactin levels than HC (CVR=1.28, 95% CI 1.02, 1.62). SMD for morning cortisol concentrations was non-significant: 0.34 (95% CI -0.01, 0.69) and no inter-group variability significant differences were detected: CVR= 1.05 (95% CI 0.91, 1.20). Meta-regression analyses for age and quality were non-significant. Funnel plots did not suggest a publication bias. CONCLUSIONS AND RELEVANCE: Increased prolactin levels were found in AN-FEP patients. A greater inter-group variability in the AN-FEP group suggests the existence of patient subgroups with different prolactin levels. No significant abnormalities were found in morning cortisol levels. Further research is needed to clarify whether prolactin concentrations could be used as an illness biomarker.

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.

Oral health and the symptoms of schizophrenia.

The objectives of this study were to evaluate the oral health of a group of schizophrenic outpatients and a control group without psychiatric illness. The study also aimed to assess the influence of positive and negative symptomatology on oral health among outpatients with schizophrenia. The DMF-T Index (sum of decayed, missing and filled teeth) and the Community Periodontal Index of Treatment Needs (CPITN) were assessed in both groups. We evaluated the psychopathological state of the patient group using the Positive and Negative Syndrome Scale (PANSS). The schizophrenic patients had higher scores than the control group with respect to decayed teeth (4.39 vs. 0.72), missing teeth (5.66 vs. 1.50), the DMF-T index (13.51 vs. 7.8) and CPITN (2.32 vs. 1.04); and lower scores for filled teeth (3.53 vs. 5.54). The PANSS negative subscale score correlated positively with the oral health variables studied, whereas the PANSS positive subscale score correlated negatively and exclusively with the number of missing teeth. Age and smoking status affected oral health in both groups, but even when the influence of these factors was considered, the oral health of the patients was poorer than that of the control group.

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.

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.