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Objective: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning., Methods: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta-analyses and other sources for drugs used in the treatment of bipolar disorder., Results: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer., Conclusion: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long-term outcomes and illness trajectory, instead of simply approaching symptom clusters., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Attention-deficit/hyperactivity disorder (ADHD) is a very common psychiatric disorder across the life cycle and frequently presents comorbidities. Since ADHD is highly heritable, several studies have focused in the underlying genetic factors involved in its etiology. One of the major challenges in this search is the phenotypic heterogeneity, which could be partly attributable to the sexual dimorphism frequently seen in psychiatric disorders. Taking into account the well-known sexual dimorphic effect observed in serotonergic system characteristics, we differentially tested the influence of HTR1B SNPs (rs11568817, rs130058, rs6296 and rs13212041) on ADHD susceptibility and on its major comorbidities according to sex. The sample comprised 564 adults with ADHD diagnosed according to DSM-IV criteria and 635 controls. There was no association of any HTR1B SNPs tested in relation to ADHD susceptibility. As for the comorbidities evaluated, after correction for multiple tests, significant associations were observed for both rs11568817 and rs130058 with substance use disorders (P corr  = 0.009 and P corr  = 0.018, respectively) and for rs11568817 with nicotine dependence (P corr  = 0.025) in men with ADHD. In women with ADHD, the same rs11568817 was associated with generalized anxiety disorder (P corr  = 0.031). The observed effects of rs11568817 G allele presence conferring risk to either substance use disorders or generalized anxiety disorder according to sex, suggest an overall scenario where a higher transcriptional activity of HTR1B, resulting from the presence of this allele, is related to externalizing behaviors in men and internalizing behaviors in women. These results are consistent with and expand previous evidence of sexual dimorphism of the serotoninergic system., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder., Methods: Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms., Results: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05)., Conclusion: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings., (© The Royal Australian and New Zealand College of Psychiatrists 2015.)

Background: During over half a century, science has shown that lithium is the most efficacious treatment for bipolar disorder but despite this, its prescription has consistently declined internationally during recent decades to approximately 35% ever use or less of patients with bipolar disorder. Content: This narrative review provides an overview of the decreasing use of lithium in bipolar disorder internationally, shortly summarises the evidence for lithium's acute and prophylactic effects in bipolar disorder, discuss the challenges in relation to lithium including side effects, long-term risks and myths around lithium and provides two detailed examples on how specialised care models may result in successful increase of the use of lithium to 70% of patients with bipolar disorder largescale and improve care regionally and nationally. Conclusions: Decades of scientific investigations and education and teaching of clinicians and the public has not increased the use of lithium on a population-based large scale. It is argued that lithium should be the drug of choice for maintenance therapy as the single first-line treatment and that organizational changes are needed with specialised care for bipolar disorder to systematically and long-term change the use of lithium on a large-scale population-level. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify clinical predictors of treatment attrition, medication choice, improvement and response to pharmacotherapy in adult attention-deficit/hyperactivity disorder (ADHD). 150 ADHD patients were enrolled and naturalistically followed-up for at least 4 months. Conners' Adult ADHD Rating Scales–Observer: Screening Version (CAARS-O:SV) were used to measure ADHD severity. 58 subjects (38.7%) were lost at follow-up, while 75 (50%) completed follow-up assessment, on average after 26.05 ± 11.99 weeks; 35 were treated with atomoxetine (ATX) and 40 with methylphenidate (MPH). Treatments were moderately effective (d = 0.72) and 37 patients (49.3%) were responders (≥30% CAARS-O:SV decrease). Patients lost at follow-up had lower inattentive symptoms, less generalised anxiety and family history of bipolar disorder, more amphetamine use disorder than follow-up completers. Compared to ATX-treated subjects, MPH-treated patients had greater severity of hyperactivity/impulsivity and were more frequently diagnosed with alcohol use disorder. While MPH and ATX showed similar efficacy, more pronounced improvements were observed in patients with combined ADHD, anxiety and substance use disorders. ADHD severity and comorbid substance use positively predicted response. Consensus-based hierarchical treatment of ADHD comorbidity is not consistently supported. Comorbid anxiety, mood and substance use disorders should not discourage the treatment of adult ADHD. [ABSTRACT FROM AUTHOR]

The topic of this narrative review is mood stabilizers. First, the author's definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author's criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with "insufficient" ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided. [ABSTRACT FROM AUTHOR]

This study cross-validated the dot counting test (DCT) as a performance validity test (PVT) in an adult attention-deficit/hyperactivity disorder (ADHD) clinical population and examined the effect of ADHD subtype and psychiatric comorbidity on accuracy for detecting invalidity. DCT performance was assessed among 210 consecutive adult ADHD referrals who underwent neuropsychological evaluation and were classified into valid (n = 175) or invalid (n = 35) groups based on seven independent criterion PVTs. The invalid group had significantly worse DCT performance than the valid group using both the standard and unrounded scoring procedure ( η p 2 =. 28). Classification accuracy was excellent, with 54.3% sensitivity/92% specificity at optimal cut-scores of ≥14 (rounded) and ≥13.38 (unrounded). Nonsignificant DCT performance differences emerged based on ADHD subtype or the presence/absence of comorbid psychopathology. The DCT functions well as a nonmemory-based PVT in an ethnoracially diverse ADHD population, supporting its clinical utility for detecting invalid neurocognitive performance during ADHD evaluations. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset condition that may continue into adulthood. When assessing adult patients, clinicians usually rely on retrospective reports of childhood symptoms to evaluate the age-of-onset criterion. Since inaccurate symptom recall may impede the diagnosis and treatment of ADHD, knowledge about the factors influencing retrospective reports is needed. This longitudinal study investigated (a) the accuracy of retrospective symptom ratings by adult participants with a childhood diagnosis of ADHD (self-ratings) and parents or significant others (proxy ratings), and (b) the influence of current ADHD symptom severity and ADHD-associated impairments on retrospective symptom ratings. Participants (N = 55) were members of the Cologne Adaptive Multimodal Treatment (CAMT) study who had been referred and treated for ADHD in childhood and were reassessed in adulthood (average age 27 years). Participants' retrospective self-ratings were substantially lower than, and did not correlate with, parents' ADHD symptom ratings provided at study entry, while retrospective symptom ratings provided by proxy respondents correlated moderately with parents' childhood ratings. In addition, participants were more likely to underreport childhood symptoms (79%) and more frequently denied the presence of three or more childhood symptoms (17%) compared to proxy respondents (65% underreporting, 10% false-negative recall). Proxy respondents' symptom recall was best predicted by childhood ADHD, while participants' symptom recall was best predicted by current ADHD symptom severity. ADHD-associated impairments were not correlated with symptom recall after controlling for childhood ADHD. Together, these findings suggest a recall bias in adult patients and question the validity of retrospective reports, even in clinical samples. [ABSTRACT FROM AUTHOR]

Impulsivity has a strong genetic component and is considered an endophenotype in many psychiatric disorders. Impulsivity in adult ADHD has become a focus of interest more recently because of its suggested prominence in this age. Objective: This study aimed to access self-reported impulsivity levels in biological parents of ADHD offspring, according to their status: non-ADHD (controls), remitted, nonremitted. Method: Impulsivity levels of 155 parents of ADHD children were compared according to their status using the Barratt Impulsiveness Scale (BIS-11). Results: The ADHD group presented the highest levels of impulsivity compared with all other groups. The remitted ADHD and control groups showed no significant differences in impulsivity levels. Conclusion: Impulsivity tended to remit alongside ADHD symptoms in remitters and to persist in those presenting with the residual form of adult ADHD suggesting it should not be considered as an endophenotype. Only the attentional dimension was impaired, cautioning against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) impulsivity proposed criteria. [ABSTRACT FROM AUTHOR]

Background: The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5′ regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. Methods: Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5′ regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. Results: Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from − 1587 to − 1371 bp (TSS, + 1), − 1149 to − 894 bp, − 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions − 603 to − 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. Conclusions: HTR1B 5′ regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions − 1587 to − 1371 bp, − 1149 to − 894 bp, − 603 to − 316 bp, − 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression. [ABSTRACT FROM AUTHOR]

Objective: To examine ADHD symptom persistence and subtype stability among substance use disorder (SUD) treatment seekers. Method: In all, 1,276 adult SUD treatment seekers were assessed for childhood and adult ADHD using Conners' Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; CAADID). A total of 290 (22.7%) participants met CAADID criteria for childhood ADHD and comprise the current study sample. Results: Childhood ADHD persisted into adulthood in 72.8% (n = 211) of cases. ADHD persistence was significantly associated with a family history of ADHD, and the presence of conduct disorder and antisocial personality disorder. The combined subtype was the most stable into adulthood (78.6%) and this stability was significantly associated with conduct disorder and past treatment of ADHD. Conclusion: ADHD is highly prevalent and persistent among SUD treatment seekers and is associated with the more severe phenotype that is also less likely to remit. Routine screening and follow-up assessment for ADHD is indicated to enhance treatment management and outcomes. [ABSTRACT FROM AUTHOR]

We identified relapse/maintenance-of-response (MOR) predictors following discontinuation of long-term atomoxetine treatment in pediatric and adult patients with attention-deficit/hyperactivity disorder (ADHD) and assessed correlations between ADHD symptoms and quality of life (QoL). Post hoc analyses of data from two randomized, double-blind, placebo-controlled, phase 3 withdrawal studies in patients with ADHD meeting predefined response criteria before randomization. Study 1: patients ( N = 163; 6-15 years) received atomoxetine (1.2-1.8 mg/kg/day) for 1 year, followed by randomization to atomoxetine ( n = 81) or placebo ( n = 82) for 6 months. Study 2: patients ( N = 524; 18-50 years) received atomoxetine (80-100 mg/day) for ~6 months, followed by randomization to atomoxetine ( n = 266) or placebo ( n = 258) for ~6 months. Placebo patients were used for the analyses. Relapse: ≥50% worsening of prerandomization improvement in ADHD symptoms and ≥2 level severity increase on the Clinical Global Impression-Severity (CGI-S) scale at 2 consecutive visits; MOR: retaining ≥75% of prerandomization symptom improvement and CGI-S ≤ 2 at all visits (study 1); retaining ≥70% of prerandomization symptom improvement and CGI-S ≤ 3 at all visits (study 2). In adults, statistically significantly ( P ≤ .05) increased likelihood of relapse was associated with prerandomization presence of Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator-Rated:Screening Version (CAARS-Inv:SV) items 'difficulty awaiting turn' and 'careless mistakes.' In pediatric patients, less MOR was associated with prerandomization presence of ADHD Rating Scale-IV-Parent Version Investigator-Rated item 'does not listen'; in adults, less MOR was associated with prerandomization presence of CAARS-Inv:SV items 'loses things' and 'difficulty awaiting turn.' Changes in patients' QoL after withdrawal from atomoxetine moderately correlated with changes in ADHD symptoms in pediatric patients and mildly in adults. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The traditional definition of Attention-Deficit/Hyperactivity Disorder (ADHD), assuming onset in childhood, has been challenged by evidence from four recent birth-cohort studies that reported most adults with ADHD lacked a childhood categorical ADHD diagnosis.Recent Findings: Late onset of symptoms was evaluated in the long-term follow-up of the Multimodal Treatment study of ADHD (MTA). In most cases, other factors were present that discounted the late onset of ADHD symptoms and excluded the diagnosis of ADHD. We offer two theoretical frameworks for understanding the ADHD trajectory throughout the life cycle: (1) the complex phenotype model, and (2) the restricted phenotype model. We conclude that (a) late onset (after age 12) is a valid trajectory for ADHD symptoms, (b) the percentage of these cases with onset after adolescence is yet uncertain, and [ABSTRACT FROM AUTHOR]

BackgroundCourse and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.MethodA 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.ResultsRetention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54–25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04–1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).ConclusionsDespite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults. [ABSTRACT FROM PUBLISHER]

Trait anxiety is a vulnerable personality factor for anxiety and depression. High levels of trait anxiety confer an elevated risk for the development of anxiety and other psychiatric disorders. There is evidence that 5-hydroxytryptamine receptor 1B (5-HT1B) gene polymorphisms play an important role in emotional disorders. Genotyping for four single-nucleotide polymorphisms (SNP) (rs11568817, rs130058, rs6297, and rs13212041) was conducted for 388 high trait anxious (HTA) individuals and 463 low traitanxious (LTA) individuals in Chinese Han college subjects. The results showed that the frequencies of the C-allele and TC + CC genotype of rs13212041 in the LTA individuals were higher than that in the HTA individuals (p = 0.025 and p = 0.014, respectively). Both the C-allele and TC + CC genotype were associated with trait anxiety decreasing (OR = 0.771 and OR = 0.71, respectively). Furthermore, different gene model analysis also showed that the C allele was a protective factor for trait anxiety in Chinese Han college subjects. These findings suggest that 5-HT1B rs13212014 may play a role in trait anxiety among China Han college subjects. The rs13212014 polymorphism may be involved in decreasing the risk of trait anxiety. These results also provide a novel insight into the molecular mechanism underlying trait anxiety. [ABSTRACT FROM AUTHOR]