Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration.

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

Parental psychological distress associated with COVID-19 outbreak: A large-scale multicenter survey from Turkey.

AIMS: Pandemics can cause substantial psychological distress; however, we do not know the impact of the COVID-19 related lockdown and mental health burden on the parents of school age children. We aimed to comparatively examine the COVID-19 related the stress and psychological burden of the parents with different occupational, locational, and mental health status related backgrounds. METHODS: A large-scale multicenter online survey was completed by the parents (n = 3,278) of children aged 6 to 18 years, parents with different occupational (health care workers-HCW [18.2%] vs. others), geographical (Istanbul [38.2%] vs. others), and psychiatric (child with a mental disorder [37.8%]) backgrounds. RESULTS: Multivariable logistic regression analysis showed that being a HCW parent (odds ratio 1.79, p < .001), a mother (odds ratio 1.67, p < .001), and a younger parent (odds ratio 0.98, p = .012); living with an adult with a chronic physical illness (odds ratio 1.38, p < .001), having an acquaintance diagnosed with COVID-19 (odds ratio 1.22, p = .043), positive psychiatric history (odds ratio 1.29, p < .001), and living with a child with moderate or high emotional distress (odds ratio 1.29, p < .001; vs. odds ratio 2.61, p < .001) were independently associated with significant parental distress. CONCLUSIONS: Parents report significant psychological distress associated with COVID-19 pandemic and further research is needed to investigate its wider impact including on the whole family unit.

Investigation of structure-function correlation among the young offspring of patients with bipolar disorder.

Bipolar disorder (BD) has been associated with impaired executive functioning and integrity of fronto-limbic white matter tracts. The evaluation of these factors in young offspring of patients with BD (BDoff) as a high-risk group offers an opportunity to investigate factors that could predict vulnerability to the disorder. This study aims to examine the correlation between neurocognition and neuroimaging findings to evaluate the potential for these findings as biomarkers for the early recognition of BD. We enrolled BDoff (n = 16) who were aged between 12 and 18. Participants were assessed using clinical and neurocognitive tests. In addition, structural brain magnetic resonance and diffusion tensor imaging data were obtained. Mean fractional anisotropy (FA) and mean diffusivity (MD) values of the superior longitudinal fasciculus (SLF) and cingulum were extracted and correlations with neuropsychological data were analyzed. FA values in the SLF were negatively correlated with Stroop interference, the Wisconsin Card Sorting Test, and the Trail Making Test (B-A) scores. MD values in the cingulum were inversely correlated with the Child and Youth Resilience Measure and positively correlated with higher scores on the Barratt Impulsiveness Scale-Attentional. These findings provide a link between features of the brain and cognitive dysfunction in BDoff.

Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate.

AIM: To examine theeffects on the brain of 2-month treatment withamethylphenidate extended-release formulation (OROS-MPH) using [Tc-99m] TRODAT-1SPECT in a sample of treatment-naïve adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). In addition, to assess whether risk alleles (homozygosity for 10-repeat allele at the DAT1 gene were associated with alterations in striatal DAT availability. METHODS: Twenty adolescents with ADHD underwent brain single-photon emission computed tomography (SPECT) scans with [Tc-99m] TRODAT-1 at baseline and two months after starting OROS-MPH treatment with dosages up to 1 mg/kg/day. Severity of illness was estimated using the Clinical Global Impression Scale (CGI-S) and DuPaul ADHD Rating Scale-Clinician version (ARS) before treatment,1 month and 2 months after initiating OROS-MPH treatment. RESULTS: Decreased DAT availability was found in both the right caudate (pretreatment DAT binding: 224.76 ±â€¯33.77, post-treatment DAT binding: 208.86 ±â€¯28.75, p = 0.02) and right putamen (pre-treatment DAT binding: 314.41 ±â€¯55.24, post-treatment DAT binding: 285.66 ±â€¯39.20, p = 0.05) in adolescents with ADHD receiving OROS-MPH treatment. Adolescents with ADHD who showed a robust response to OROS-MPH (n = 7) had significantly greater reduction of DAT density in the right putamen than adolescents who showed less robust response to OROS-MPH (n = 13) (p = 0.02). However, between-group differences by treatment responses were not related with DAT density in the right caudate. Risk alleles (homozygosity for the 10-repeat allele of DAT1 gene) in the DAT1 gene were not associated with alterations in striatal DAT availability. CONCLUSION: Two months of OROS-MPH treatment decreased DAT availability in both the right caudate and putamen. Adolescents with ADHD who showed a robust response to OROS-MPH had greater reduction of DAT density in the right putamen. However,our findings did not support an association between homozygosity for a 10-repeat allele in the DAT1 gene and DAT density, assessedusing[Tc-99m] TRODAT-1SPECT.

Atomoxetine treatment may decrease striatal dopaminergic transporter availability after 8 weeks: pilot SPECT report of three cases.

Attention deficit/hyperactivity disorder is one of the most common neurodevelopmental disorders. The pathophysiology is thought to involve noradrenaline and dopamine. The role of dopamine transporter (DAT) was evaluated in imaging studies using mostly dopamine reuptake inhibitors. Atomoxetine is a selective noradrenaline reuptake inhibitor. Here we report the results of a pilot study conducted to evaluate changes in striatal DAT after 8 weeks of atomoxetine treatment. Our results suggest that 8 weeks of atomoxetine treatment may change striatal DAT bioavailability as measured via SPECT but that change was not correlated with genotype or clinical improvement.

Effects of long-term methylphenidate treatment: a pilot follow-up clinical and SPECT study.

BACKGROUND: Although abnormalities in the regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment have been reported in children with attention deficit hyperactivity disorder (ADHD), there are few prospective longitudinal studies assessing the long-term effects of MPH and discontinuation effects after chronic treatment. METHODS: The authors studied ten drug-naive children (2 girls, 8 boys, mean age+/-S.D.=9.60+/-1.96) diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria, using (99m)Tc-HMPAO-single photon emission computed tomography (SPECT). Patients were studied at baseline (visit 1), after 2 months of MPH treatment (visit 2) and after a drug-free period of 2 months following 12 months of MPH treatment (visit 3) at doses of 1 mg/kg/day. We evaluated SPECT data visually and semi-quantitatively. RESULTS: Two months of chronic MPH treatment resulted in visually detectable improvement in hypoperfusion in the right frontal cortex and all areas of temporal cortex with the exception of left lateral temporal cortex. This improvement was still detectable on visual evaluations of SPECT data after 2 months of treatment discontinuation. The treatment effects that were detected visually were not statistically significant in semi-quantitative analyses. CONCLUSIONS: Treatment effects of chronic MPH treatment may persist long after the discontinuation of the treatment.