Effects of the dopamine transporter gene on neuroimaging findings in different attention deficit hyperactivity disorder presentations.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a phenotipically and neurobiologically heterogeneous disorder. Deficiencies at different levels in response inhibition, differences in dopamine transporter genotype (DAT1) and various symptomatic presentations contribute to ADHD heterogeneity. Integrating these three aspects into a functional neuroimaging research could help unreval specific neurobiological components of more phenotipically homogeneous groups of patients with ADHD. During the Go-NoGo trial, we investigated the effect of the DAT1 gene using 3 T MRI in 72 ADHD cases and 24 (TD) controls that typically developed between the ages 8 and 15 years. In the total ADHD group, DAT1 predicted homozygosity for the 10R allele and hypoactivation in the anterior cingulate cortex and paracingulate cortex. There were no significant activation differences between DAT1 10R/10R homozygotes and 9R carriers in TD controls. Subjects with predominantly inattentive ADHD (ADHD-I) presentation with DAT1 10R/10R homozygous reduced neuronal activation during Go trial particularly in the frontal regions and insular cortex, and in the parietal regions during NoGo trial (brain regions reported as part of Default Mode Network- DMN). Additionally, DAT1 10R/10R homozygousness was associated with increased occipital zone activation during only the Go trial in the ADHD combined presentation (ADHD-C) group. Our results point the three main findings: 1) The DAT1 gene is 10R homozygous for differentiated brain activation in ADHD cases but not in the TD controls, supporting the DAT1 gene as a potential marker for ADHD, 2) The relationship between the DAT1 gene and the occipital regions in ADHD-C group which may reflect compensatory mechanisms, 3) The relationship between DAT1 gene and the reduced DMN suppression for 9R carriers probabaly stems from the ADHD-I group.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo

Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo.

OBJECTIVE: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3'-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). METHODS: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. RESULTS: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. CONCLUSION: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

Development of a Giant Cornu Cutaneum in a Patient with a Coincidental Foreknown Intracranial Meningioma.

The diagnostic spectrum for scalp lesions is extensive and comprises either benign or malignant features. Cornu cutaneum (CC) is a well-recognized condition; however, its origin and natural course are not always obvious. We present the case of a 78-year-old male patient who was diagnosed with intracranial meningioma in 2014 and who subsequently refused treatment. He presented a new scalp lesion, resembling a horn, in the vertex region 1.5 years after his last follow-up. The lesion was excised, and the patient was histopathologically diagnosed as having CC caused by squamous cell carcinoma. CC can be easily recognized when it resembles animal horn; however, it can assume different shapes that require a physician to be vigilant. Moreover, a lesion’s benign or malignant nature is not obvious in all cases. Hard, protruding scalp lesions should be examined for CC, and a histopathological evaluation should be performed to make a definitive diagnosis.

Comparisons between sluggish cognitive tempo and ADHD-restrictive inattentive presentation phenotypes in a clinical ADHD sample.

There is a debate how different ADHD cases with a comorbid sluggish cognitive tempo (SCT) phenotype are from subjects with a pure inattentive ADHD presentation (ADHD-restrictive inattentive presentation). In this study, 214 patients aged 8-15 years from an ADHD outpatient clinic were assessed, and 100 typically developing controls (TD) were recruited as comparisons. No psychiatric comorbidities except for oppositional defiant disorder were allowed. We compared 29 cases with ADHD + SCT with 34 ADHD-RI cases and 92 TD subjects on sociodemographic profiles, CBCL subscales scores and neurocognitive findings. Regarding sociodemographic profiles (age, gender and parental education) and CBCL subscales, ADHD + SCT and ADHD-RI cases did not differ in any score (all p > 0.05). Comparing with SCT cases, ADHD-RI cases presented slower psychomotor speed and worse neurocognitive index (p < 0.001). We found that only SCT was independently associated with a lower performance in total memory score. ADHD-RI was independently associated with longer reaction time. Our findings suggest that although SCT might be expected to present longer reaction time, we found that slower psychomotor speed and longer reaction time scores were related to inattention. Overall, SCT and ADHD-RI groups were distinguished by differential associations with measures of memory and reaction time.

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Is a Risk Factor for Attention-Deficit Hyperactivity Disorder in a Turkish Sample.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. METHODS: Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher's Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms. RESULTS: The GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes. CONCLUSION: We found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.

Altered structural connectivity is related to attention deficit/hyperactivity subtypes: A DTI study.

This study aimed to provide novel insights into the white matter (WM) microstructural properties of Attention Deficit/Hyperactivity Disorder (ADHD) subtypes by recruiting a relatively large sample of stimulant-naïve children and adolescents who had no comorbidity other than Oppositional Defiant Disorder and were homogenous according to the DAT1 gene polymorphism. A sample of 72 ADHD subjects and 24 controls aged 8-15 years were enrolled in the study. We applied tract-based spatial statistics to the DTI measures for obtaining fractional anisotropy (FA) and axial, radial diffusivity (AD, RD) measures to explore ADHD type-related differences in WM for the whole brain. Comparing ADHD-Combined group (ADHD-C) with the ADHD predominantly inattentive group (ADHD-I) we detected increased RD in several bilateral brain area and increased AD mostly in left side of the brain, including the body and splenium of the corpus callosum; the anterior and posteriors limbs of the internal capsule; the superior, anterior and posterior corona radiata; the posterior thalamic radiation; and the superior longitudinal fasciculus. Likewise, mostly in the overlapping brain areas, the ADHD-C group presented increased AD values than ADHD-RI. Significant differences among ADHD types could be a preliminary evidence that they have distinct microstructural properties. There were no significant differences in diffusivity between controls and both the ADHD group as whole or any ADHD subgroups.

The Human Tail: A Simple Skin Appendage or Cutaneous Stigma of an Anomaly?

AIM: The human tail is a term to describe skin-covered protrusions in the lumbosacral and coccygeal region, ascribing to the resemblance to the tails in the animals. The first reports dates back to second half of the 19th century, the etiological bases could not been ascertained yet. They are mainly classified as true or pseudo-tails. MATERIAL AND METHODS: Five cases with human tails were diagnosed and managed in our hospital between 2010 and 2014. Their demographic and lesion characteristics are presented. RESULTS: Three of the 5 cases were male patients. The ages ranged between 1 day and 50 years at the time of diagnosis. The patients were diagnosed basically by the external appearance of the lesions without neurological deficits. Detailed examination revealed several associated lesions: two dermal sinus tracts, one tethered spinal cord and one club-foot in one-day preemie. Two patients had true and 3 had pseudo-tails. Four of them underwent surgery but the last one did not accept surgery. Surgery consisted of simple excision of the lesion in 2 patients with true tails and excision and removal of dermal sinus tract and untethering when necessary in the other 2 pseudo-tails. CONCLUSION: The presented study indicated that true human tails are simple skin appendages without any associated spinal anomalies. However, pseudo-tails are potentially complex lesions with a high risk of spinal dysraphisms; warranting further diagnostic work-up and more extensive surgical technique if necessary. The key to managing human tails is making a clear distinction between true tails and pseudo-tails.

Decreasing ADHD phenotypic heterogeneity: searching for neurobiological underpinnings of the restrictive inattentive phenotype.

During the process of developing the DSM-5, a new phenotype of ADHD was proposed-the ADHD restrictive inattentive presentation (ADHD-RI), describing subjects with high endorsement of inattentive symptoms and a low level of hyperactivity. However, this phenotype was not included in the DSM-5 because of the lack of robust neurobiological data. We aimed to assess the specific neurobiological underpinnings of individuals presenting ADHD-RI. We compared a sample of 301 subjects (101 ADHD-Combined; 50 ADHD-RI; 50 ADHD predominantly inattentive type and 100 typically developing subjects) aged 8-15 years, using a complete neuropsychological battery, molecular genetic data (DRD4 and DAT1 most studied polymorphisms) and functional MRI during a Go-No/Go task. Subjects with ADHD-RI had a significantly different neuropsychological profile compared with the other groups, including lower psychomotor speeds, longer reaction times and the worst overall performance in the global neurocognitive index. The proportion of subjects with the presence of DRD4-7 repeat allele was significantly higher in ADHD-RI. The fMRI data suggested that more attention-related posterior brain regions (especially temporo-occipital areas) are activated in ADHD-RI during both Go and No-Go cues compared to TD controls and ADHD predominantly inattentive type. ADHD-RI may represent a different phenotype than other types of ADHD. In addition, our results suggest that reducing the phenotypic heterogeneity may aid in the search for the neurobiological underpinnings of ADHD.

The natural course and factors affecting severity of Behçet's disease: a single-center cohort of 368 patients.

Our goal was to determine, retrospectively, the occurrence of the symptoms of Behçet's disease in chronological order and the course of the disease. Additionally, probable factors affecting the clinical severity were investigated. A total of 368 patients (171 females and 197 males; aged 41.11 ± 10.9 years) were included in this retrospective cohort study. The chronological order of the clinical manifestations was recorded. Patients were also assessed for clinical severity score. Oral ulcer was the most common manifestation (100 %) followed by genital ulcer (89.4 %), papulopustular lesions (75 %) and articular involvement (60.1 %). Oral ulcer was the most common onset manifestation (66.8 %) followed by genital ulcer (4.9 %), erythema nodosum (3.3 %) and ocular involvement (1.4 %). The duration between the onset symptom and the fulfillment of the diagnostic criteria was 4.67 ± 5.9 years. The duration between the time point of fulfillment of diagnostic criteria and the diagnosis (2.5 ± 2.1 years) was longer in patients having only mucocutaneous lesions (2.8 ± 2.2 years) than in patients having serious organ involvements (1.9 ± 1.6 years; p < 0.01). Serious involvements such as neurological involvement and large vessel involvement had their onsets later. Mean clinical severity score was higher in male patients (5.3 ± 2.1 vs 4.8 ± 1.7; p < 0.05). In logistic regression analysis, male gender (p = 0.03) and increased number of symptoms at diagnosis (p < 0.001, R (2) = 0.73) were found to be significant risk factors for severity. Mucocutaneous lesions, especially oral and/or genital ulcers, usually precede possible serious involvements; therefore, careful follow-up is mandatory. Males with increased number of organ involvements at the diagnosis are associated with more severe disease.

Incidence and clinical significance of lesions presenting as a scalp mass in adult patients.

BACKGROUND: Lesions initially presenting as a scalp mass are quite common entities with a wide spectrum of causes. They may be directly related to the scalp itself or may be secondary stigmata of an underlying process in the skull. The rate and clinical significance of the differential diagnosis of these lesions are not well studied in the adult population. METHODS: Three hundred sixty patients were operated on for scalp masses at our hospital between January 2011 and February 2014. The patients were defined retrospectively by using the hospital coding system for scalp lesions. Among these patients, 15 were excluded for being younger than 16 years old. RESULTS: A total of 345 patients, consisting of 172 females (49.9 %) and 173 males (50.1 %), were included in the study. The mean age at diagnosis was 44.3 (16-89). There were no mortalities during the follow-up period (mean 17.99 months). Mean numbers of scalp lesions and surgeries were 1.25 and 1.18, respectively. There were 32 distinct histopathological diagnoses, the 5 most common being trichilemmal cyst, epidermal cyst, lipoma, nevus and sebaceous cyst in order of frequency. The rate of "clinically significant" pathologies, meaning malignancies or those needing follow-up, was around 7.8 %. The incidence of correct preoperative diagnosis with respect to the departments was 13-27 %. CONCLUSIONS: Our series indicated that generally scalp masses were underestimated and detailed preoperative diagnostic workup or interdisciplinary consultations were not performed regularly. The overall incidence of clinically significant lesions warrants a high degree of vigilance for accurate diagnosis and management of these lesions, because their etiology can be so variable and challenging.

Relationship between periodontal findings and Behçet's disease: a controlled study.

BACKGROUND: Behçet's disease (BD) is a chronic, relapsing, systemic vasculitis of unknown aetiology. The involvement of oral mucosal surfaces represents the onset feature of the disease in the majority of patients. OBJECTIVE: The aim of this study was to evaluate the periodontal status of BD patients and then compare with recurrent aphthous stomatitis (RAS) patients and healthy controls. We also determined the relationship between the periodontal condition and the clinical severity of the disease in BD patients. METHODS: Eighty-six patients with BD, 63 patients with RAS and 82 healthy subjects were included in the study. The periodontal status of all subjects was evaluated according to the community periodontal index of treatment needs (CPITN). BD patients were also assessed for clinical severity score (CSS) as described previously. RESULTS: The mean CPITN were observed to be higher in BD patients (1.79 +/- 0.96) compared with RAS patients (1.22 +/- 0.87) and healthy controls (1.18 +/- 0.98) (p<0.001). There was a positive association between CSS and CPITN (p=0.017) in BD patients. CONCLUSION: Our results showed that periodondal status is worse in BD patients and associated with disease severity. We can speculate that periodontitis may induce a systemic inflammatory process that may contribute to the development and/or progression of BD.

Specific interleukin-1 gene polymorphisms in Turkish patients with Behçet's disease.

Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. The pro-inflammatory cytokine interleukin-1 (IL-1) has been implicated in the pathogenesis of BD. Our aim was to determine a possible association of specific polymorphisms of IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes with susceptibility for BD. We genotyped 72 patients with BD and 163 healthy controls for IL-1alpha-889, IL-1beta-511, and +3953 (nt5887) single-nucleotide polymorphisms besides IL-1 receptor antagonist variable number of tandem repeat polymorphism (for five different alleles). Comparison of the IL-1beta+3953 T allele and TT genotype frequencies showed a significant difference between patients with BD and controls (54.2 vs. 40.5%, OR = 1.74, P = 0.024, and 40.3 vs. 19.6%, OR = 2.76, P = 0.009, respectively). However, no difference was observed in the genotype or allele frequencies of IL-1alpha-889, IL-1beta-511, and IL-1 receptor antagonist between the patients with BD and the controls. Our results indicate that susceptibility to BD is increased in individuals carrying the IL-1beta+3953 T allele and TT genotype.

Review of the chronology of clinical manifestations in 60 patients with Behçet's disease.

BACKGROUND: The natural course of Behçet's disease is not fully known. OBJECTIVE: The aim of the present study was to determine the occurrence of the symptoms retrospectively in chronologic order in patients with Behçet's disease, diagnosed according to the criteria of the International Study Group for Behçet's Disease. METHODS: A total of 60 consecutive patients (29 male and 31 female; aged 35.87 +/- 9.84 years) were involved in the study. The symptoms of the disease were retrospectively recorded in the time order of the manifestations per patient. RESULTS: Oral ulcer was the most commonly observed onset manifestation (51 of 60 patients: 85%), followed by genital ulcer (13 of 60 patients: 21.7%) and articular symptoms (10 of 60 patients: 16.7%). The duration between the oral ulcer and the fulfillment of diagnostic criteria was calculated to be 3.77 +/- 4.43 years. The same duration was 2.50 +/- 4.74 and 2.11 +/- 3.44 years for genital ulcer and articular symptoms, respectively. The duration between the time point of fulfillment of diagnostic criteria and the diagnosis (2.83 +/- 2.3 years) was found to be longer in female patients (3.2 +/- 2.5 years). The duration was also longer in patients having only mucocutaneous lesions (3.18 +/- 2.5 years) than in patients having serious organ involvement such as eye disease (1.63 +/- 0.7 years; p < 0.05). CONCLUSION: Our study indicates that oral ulcer is the onset manifestation in the majority of the patients and the disease is often diagnosed with a delay of several years after the appearance of the onset sign.