Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1, and Prolactin.

BACKGROUND: Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases. OBJECTIVE: This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1), and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD), and healthy controls. METHODS: Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units, and 22 healthy controls. Diagnostic evaluations followed established criteria, and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods. RESULTS: Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha, and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls. CONCLUSION: The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.

Quantitative EEG in the Differential Diagnosis of Dementia Subtypes.

OBJECTIVE: Most neurodegenerative dementias present with substantial overlap in clinical features. Therefore, differential diagnosis is often a challenging task necessitating costly and sometimes invasive diagnostic procedures. A promising, non-invasive and cost-effective method is the widely available electroencephalography (EEG). METHODS: Twenty-three subjects with Alzheimer's disease (AD), 28 subjects with dementia with Lewy bodies (DLB), 15 subjects with frontotemporal dementias (FTDs), and 22 healthy controls (HC) were enrolled. Nineteen channel computerized EEG recordings were acquired. Mean relative powers were calculated using the standard frequency bands. Theta/alpha ratio (TAR), theta/beta ratio (TBR), a spectral index of (alpha + beta)/(theta + delta) and an alpha reactivity index (alpha in eyes-open condition/alpha in eyes-closed condition) were also calculated. Receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy. RESULTS: For the comparison of EEG measures across groups, we performed a multivariate ANOVA followed by univariate ANOVAs controlling for the effects of age, with post hoc tests. Theta power and TBR were increased in DLB compared to other groups. Alpha power was decreased in DLB compared to HC and FTD; and in AD compared to FTD. Beta power was decreased in DLB compared to AD and HC. Furthermore, regional analyses demonstrated a unique pattern of theta power increase in DLB; affecting frontal, central, parietal, occipital, and temporal regions. In AD, theta power increased compared to HC in parietal, occipital, and right temporal regions. TAR was increased in DLB compared to other groups; and in AD compared to HC. Finally, alpha reactivity index was higher in DLB compared to HC and FTD. In AD, EEG slowing was associated with cognitive impairment, while in DLB, this was associated with higher DLB characteristics. In the ROC analyses to distinguish DLB from FTD and AD, measures of EEG slowing yielded high area under curve values, with good specificities. Also, decreased alpha reactivity could distinguish DLB from FTD with good specificity. EEG slowing in DLB showed a diffuse pattern compared to AD, where a posterior and temporal slowing predominated. CONCLUSION: We showed that EEG slowing was satisfactory in distinguishing DLB patients from AD and FTD patients. Notably, this slowing was a characteristic finding in DLB patients, even at early stages, while it paralleled disease progression in AD. Furthermore, EEG slowing in DLB showed a diffuse pattern compared to AD, where a posterior and temporal slowing predominated. These findings align with the previous evidence of the diencephalic dysfunction in DLB.

A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer's disease, dementia with Lewy bodies and Frontotemporal dementia.

BACKGROUND: Here, we aimed to investigate the roles of long-term potentiation-like (LTP-like) plasticity using intermittent theta burst (iTBS) protocol and resting motor threshold (rMT) in the differential diagnosis of Alzheimer's disease (AD), diffuse dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). METHOD: We enrolled 21 subjects with AD, 28 subjects with DLB, 14 subjects with FTD, and 33 elderly subjects with normal cognitive functions into the study. We recorded rMT and percentage amplitude change of motor evoked potentials (MEPs) after the iTBS protocol in each group. RESULTS: In patients with AD and DLB, the percentage amplitude change of MEPs, and rMTs were significantly lower than in healthy subjects. However, no significant difference was observed in individuals with FTD. CONCLUSION: Our findings showed that transcranial magnetic stimulation measures, particularly rMTs and LTP-like plasticity, may be potential biomarkers to distinguish between different dementia subtypes. Impaired motor cortical excitability and synaptic plasticity were more prominent in AD and DLB than in FTD. This aligns with the evidence that cortical motor networks are usually spared in FTDs in early-to-middle stages.

Atypical findings: Atypical parkinsonian syndromes or Atypical parkinsonian syndromes look-alikes.

OBJECTIVE: In parkinsonian syndromes, presentations other than current diagnostic criteria are considered atypical findings. Our goal was to identify and describe the frequency and features of uncommon manifestations of atypical parkinsonian syndromes within our group. METHODS: We retrospectively retrieved the medical records of all patients admitted to our clinic with parkinsonism between January 2011 and January 2022. We only included patients with atypical parkinsonian syndromes, in which the diagnosis was based on current clinical criteria. We retrospectively analyzed neurological, psychiatric, radiological, and electrophysiological characteristics. Typical and atypical features were classified according to the current clinical criteria and previous reports. RESULTS: We determined 51 patients with atypical parkinsonian syndromes; 46 were included, whereas five were excluded due to insufficient follow-up. The probable diagnoses were multiple system atrophy (MSA, n = 19), dementia with Lewy bodies (DLB, n = 10), frontotemporal dementia (FTD, n = 10), corticobasal syndrome (CBS, n = 3), progressive supranuclear palsy (PSP, n = 4). The prevalence of atypical findings was similar among different types of atypical parkinsonian syndromes (p = 0.847). Atypical findings were eyelid myoclonus, double vision in MSA; ataxia, myoclonus, and a typical hummingbird sign on MRI in DLB; pyramidal findings and family history in FTD; early onset, family history, and onset with psychiatric findings in PSP-like phenotype. Genetic causes were identified in the FTD-like phenotype with pyramidal findings, whereas symptom onset was early with myoclonus in the PSP-like phenotype. CONCLUSION: Atypical findings such as abnormal saccades, myoclonus, and ataxia may be a part of degenerative syndromes. However, family history, onset at an earlier age, and specific neurological findings suggest genetic syndromes.

Three-Year Prognosis of Late-Life Depression in an Outpatient Geriatric Psychiatry Clinic: Medical Comorbidities Worsen Outcomes.

Depression is one of the most important reasons for psychiatric referrals in elderly patients. Geriatric depression can be chronic and is associated with an increased risk of dementia. We aimed to determine the prognosis of major depression patients and associated risk factors regarding persistence of depression. Patients who were admitted to the tertiary geriatric psychiatric outpatient unit of Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul between January and December 2018 and were diagnosed with major depression according to DSM-5 diagnostic criteria were included in the study. A structured telephone interview was conducted with between February-April 2022. For detailed clinical evaluation, Turkish version of Structured Clinical Interview for DSM-5-Disorders/Clinician Version (SCID-5/CV-TR), Telephone Cognitive Screen (T-cogS-TR), Geriatric Depression Scale (GDS), Clinical Dementia Rating Scale (CDR), Lawton-Brody Instrumental Activities of Daily Living Scale (IADL) and Beck Anxiety Inventory (BAI) were used. Of the 123 patients interviewed, 40.9% were diagnosed with major depression and 14.6% with minor depression. 43.4% showed significant anxiety and depression symptoms. Dementia developed in 14.6% of the patients. Only 29.5% of the patients recovered completely. Hypertension, orthopedic disease or arthritis, cancer, and absence of prior work experience were found to be predictors of current depression diagnosis. Geriatric depression has an unfavorable prognosis despite continued antidepressant treatment and may even serve as a prodrome for future dementia. Timely management of co-morbid medical conditions such as hypertension can potentially improve the prognosis of geriatric depression.

Risk of impulse control disorders in patients with Cushing's disease: do not blame cabergoline but do not give up caution.

PURPOSE: To asses risk of new-onset impulse control disorders (ICDs) in patients with Cushing's disease (CD) who initiated cabergoline (CBG) and to determine frequency of ICDs in CBG-treated patients with CD. METHODS: This naturalistic observational study had prospective and cross-sectional arms which included patients at five referral centers based in Istanbul. Patients who were scheduled for CBG were assigned to prospective arm. These patients underwent neuropsychological tests (Barratt Impulsiveness Scale, Minnesota Impulsive Disorders Interview, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Go/No-Go Task, Iowa Gambling Task, and Short Penn Continuous Performance Test) for assessment of impulsivity and psychiatric evaluations at baseline, 3, 6, and 12 months of CBG treatment. Impulsivity and new-onset ICDs were prospectively assessed. Patients with CD with current CBG treatment for ≥ 3 months and matched CBG-naïve patients with CD were included in cross-sectional arm. These patients underwent the same neuropsychological and psychiatric assessments. The impulsivity and frequency of ICDs were compared between CBG-treated and CBG-naïve patients with CD. RESULTS: The follow-up duration of prospective cohort (n = 14) was 7.3 ± 2.3 months. One patient developed major depressive episode and another patient developed compulsive gambling after CBG. We observed no significant changes in impulsivity scores during follow-up. In cross-sectional arm, CBG-treated (n = 34) and CBG-naïve patients (n = 34) were similar in impulsivity scores and frequency of ICDs [3 patients (8.8%) vs. 2 patients (5.9%) respectively, p = 1.0]. CONCLUSION: CBG-treated patients with CD appeared to have a low risk of ICDs, suggesting that CBG still holds promise as a safe agent in CD.

A Genetic Assessment of Dopamine Agonist-Induced Impulse Control Disorder in Patients With Prolactinoma.

CONTEXT: Dopamine agonist (DA)-induced impulse control disorder (ICD) represents a group of behavioral disorders that are increasingly recognized in patients with prolactinoma. OBJECTIVE: We aimed to examine the genetic component of the underlying mechanism of DA-induced ICD. METHODS: Patients with prolactinoma receiving dopamine agonist (cabergoline) treatment were included in the study. These patients were divided into 2 groups: patients who developed ICD due to DA and patients who did not. Patients were evaluated for polymorphisms of the DRD1, DRD3, COMT, DDC, GRIN2B, TPH2, OPRK1, OPRM1, SLC6A4, SLC6A3, HTR2A genes. RESULTS: Of the 72 patients with prolactinoma using cabergoline, 20 were diagnosed with ICD. When patients with and without ICD were compared according to genotype frequencies, OPRK1/rs702764, DRD3/rs6280, HTR2A/rs6313, SLC6A4/rs7224199, GRIN2B/rs7301328, TPH2/rs7305115, COMT/rs4680, DRD1/rs4532 polymorphisms significantly increased in patients with DA-induced ICD. CONCLUSION: Our results show that multiple neurotransmission systems affect DA-induced ICD in patients with prolactinoma.

Willingness to get the COVID-19 vaccine among patients with rheumatic diseases, healthcare workers and general population in Turkey: a web-based survey.

OBJECTIVES: Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population. METHODS: We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated. RESULTS: We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p < 0.001). On the other hand, hospital workers were significantly more willing (yes: 52.5%, no: 20.9% and unsure: 26.6%) (p < 0.001). Main concerns were probable side effects, unknown scientific results and having no trust. Being male, older age, working in a hospital, not having contracted COVID-19 and high scores on CAS were found to be independently associated with willingness. CONCLUSIONS: The low rate of vaccine acceptance among patients with RD, as well as general population sampling is worrying. Healthcare policies should aim to implement communication, promote confidence and increase demand for COVID-19 vaccine.

Coronavirus Pandemic: Mood Statuses of Renal Transplant Recipients During Social Isolation and Lockdown Periods.

OBJECTIVES: In an attempt to control the new coronavirus pandemic, many countries have taken unprecedented measures, such as extensive social distancing and total lockdowns of cities. Kidney transplant recipients have an increased risk for infectious diseases, including viral infections. In this study, we aimed to investigate the effects of population-wide infection control measures on the mood statuses of kidney transplant recipients. MATERIALS AND METHODS: We used an electronic survey tool to collect demographic and sociocultural data. Additionally, in the same survey, we used 2 questionnaires (the Profile of Mood States and the Hospital Anxiety and Depression Scale) to measure mood statuses of kidney transplant recipients. We also examined a control group and selected eligible participants according to age- and sex-based propensity score matching. RESULTS: We analyzed the data of 308 participants: 154 kidney transplant recipients (mean age of 39.9 ± 10.6 years; 57.1% male) and 154 control participants (mean age of 39.1 ± 10.5; 57.1% male). With regard to the Profile of Mood States questionnaire, total scores and all subscale scores, excluding vigor, were significantly lower in kidney transplant recipients than in the control group, a finding consistent with a better mood status. We found similar findings in anxiety and depression scores for the Hospital Anxiety and Depression Scale questionnaire. CONCLUSIONS: Kidney transplant recipients seem to be resilient to the psychological stress induced by social distancing and lockdown periods. Strict adherence to infection control measures is purposefully suggested in this infection-prone population.

Characteristics and outcomes of COVID-19 inpatients who underwent psychiatric consultations.

Patients hospitalized with COVID-19 are at risk of developing many neuropsychiatric disorders, due to the effects of the disease on the brain and the psychosocial pressures of having the disease. The aim of the present study was to evaluate the characteristics and outcomes of patients who were hospitalized with a diagnosis of COVID-19, who underwent psychiatric consultations. The medical records of 892 patients hospitalized due to COVID-19 and the 89 among them who requested psychiatric consultations were analyzed retrospectively. After the psychiatric consultations, patients were most frequently diagnosed with delirium (38.2 %), adjustment disorder (27.0 %), depressive disorder (19.1 %) and anxiety disorder (11.2 %). Patients with delirium had longer hospital stays (p < 0.001), were transferred more frequently to intensive care units (p < 0.001), and had higher mortality rates during their hospital stays (p < 0.001), than all other patients. The need for oxygen (p < 0.001) and mechanical ventilation (p < 0.001) was also significantly higher in delirium patients, as well as in patients who received other psychiatric diagnoses. Neuropsychiatric disorders develop in patients receiving inpatient treatments in COVID-19 wards, and these disorders negatively affect the prognosis of COVID-19. Our findings suggest that the presence of neuropsychiatric disorders in in-patients with COVID-19 might be associated with the negative outcomes of the disease.

Psychiatric morbidity and protracted symptoms after COVID-19.

We investigated the psychiatric symptomatology and the protracted symptoms in patients who had recovered from the acute COVID-19 infection. Two hundred and eighty-four patients completed a web-based or a paper survey on socio-demographic and clinical data. The psychiatric status was assessed using Impact of Events Scale-Revised (IES-R), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), and MINI suicidality scale. Patients completed a checklist for the protracted symptoms that were experienced after the acute infection. After a mean of almost 50 days following the diagnosis, 98 patients (34.5%) reported clinically significant PTSD, anxiety, and/or depression, with PTSD being the most common condition reported (25.4%). One hundred and eighteen patients (44.3%) reported one or more protracted symptom(s). Predictors of PTSD symptom severity were the female gender, past traumatic events, protracted symptoms, stigmatization, and a negative view on the COVID-19 pandemic. PTSD symptom severity was the sole independent predictor of the protracted symptoms. Our results suggest that COVID-19 patients are prone to substantial psychological distress in the first few months after the infection. The protracted symptoms were frequent in this period, and these were closely related to the posttraumatic symptoms.

Patients with acromegaly might not be at higher risk for dopamine agonist-induced impulse control disorders than those with prolactinomas.

OBJECTIVE: To evaluate the prevalence of impulse control disorders (ICD) and psychiatric symptoms in patients with acromegaly receiving dopamine agonists (DA) in comparison with those with prolactinoma, nonfunctioning pituitary adenomas (NFA), and healthy controls (HC). DESIGN: Forty patients with acromegaly, 40 with prolactinoma, 38 with NFA, and 32 HCs were included. All patients and controls were evaluated using the revised version of the Minnesota Impulsive Disorders Interview (MIDI-R), Symptom Check List (SCL-90-R) questionnaire, Barratt Impulsiveness Scale (BIS-11), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: We detected ICD associated with DAs in two patients with acromegaly (5%) and three patients (7.5%) with prolactinoma. All patients' symptoms resolved after discontinuation of the drug. While the mean DA dose was higher in patients with acromegaly than prolactinomas (p < 0.05), no difference was detected in terms of ICD prevalence between two groups (p > 0.05). SCL-90 depression and interpersonal sensitivity subscale positivity was higher in patients with NFA than HCs. Patients with prolactinoma had higher obsession and interpersonal sensitivity positivity and those with NFA had higher somatization, interpersonal sensitivity, and depression positivity as compared to patients with acromegaly (p < 0.05 for all). CONCLUSIONS: Although DA dose was significantly higher in patients with acromegaly, there was no significant difference in the prevalence of DA-related ICD. The higher prevalence of positive screening in SCL-90 in patients with NFA in comparison to HCs supports the hypothesis that the presence of a pituitary adenoma per se might cause significant psychiatric symptoms.

The psychological state and changes in the routine of the patients with rheumatic diseases during the coronavirus disease (COVID-19) outbreak in Turkey: a web-based cross-sectional survey.

We hypothesized that patients with rheumatic diseases (RD) would have increased psychological distress during the COVID-19 outbreak; therefore, assessed their psychological symptoms and changes in their routine. A web-based questionnaire survey was conducted in a cross-sectional design in three groups of participants: (1.) patients with RD, (2.) hospital workers, and (3.) high-school teachers/academic staff. Psychiatric status was evaluated using Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised scale. Overall response rate was 34.7%. We studied 771 patients with RD, 535 hospital workers, and 917 teachers/academic staff. Most of the patients with RD were unwilling to go to the hospital (86%), while 22% discontinued their medications. Biological DMARDS were the most frequent drugs whose doses were altered. Only 4% were willing to take hydroxychloroquine for protection. Moreover, the frequency of anxiety (20%), depression (43%), and post-traumatic stress (28%) among patients with RD were found to be comparable to that found among the teachers/academic staff (23%, 43% and 29%, respectively), whereas significantly less than that observed among the hospital workers (40%, 62%, and 46%, respectively) (p < 0.001). Female gender, use of social media, having a comorbid disease, or a psychiatric disorder were found to be independently associated with psychiatric symptoms in total study population. The majority of the patients were unwilling to attend outpatient visits and one-fifth skipped or stopped their immunosuppressive agents. Psychiatric symptoms in patient's and teacher's populations were of considerable clinical concern, despite being significantly lower than that observed among the hospital workers.

Are emotion recognition deficits in patients with schizophrenia states or traits? A 6-month follow-up study.

BACKGROUND: Patients with schizophrenia were found to be less successful at emotion recognition tasks (ERTs) than healthy individuals. There is a debate surrounding whether this deficit is permanent or temporary. The current study aims to assess how emotion recognition skills are affected by treatment processes and during the course of the disease and also to determine the relation of this change with clinical assessment scales, other cognitive functions, and quantitative electroencephalography (QEEG). MATERIALS AND METHODS: Twenty-four inpatients with treatment-resistant schizophrenia have been included in the study. Patients were assessed before beginning clozapine and 6 months later. During both assessments, clinical evaluation scales (Positive and Negative Syndrome Scale and Global Assessment of Functioning), Cambridge Neuropsychological Test Automated Battery (CANTAB) for schizophrenia which is used for assessment of cognitive functions were used. Electroencephalography (EEG) monitorings were performed only once before treatment. In this study, CANTAB ERT was used for emotion recognition. RESULTS: There was no statistically significant change in the emotion recognition when the first and final ERTs were compared. There was a moderately positive relationship between emotional recognition and functioning (r = 0.65, P < 0.05). Cognitive functions such as visual memory, attention, flexible thinking, and planning were found to be in correlation with emotion recognition. Furthermore, slow waves such as delta and theta activities obtained from frontal, temporoparietal, and occipital regions were associated with emotion recognition. CONCLUSION: The current study supports that emotion recognition deficits are long-term stable features of schizophrenia, slow-wave electrical activity in the frontal, temporoparietal, and occipital areas in QEEG, and cognitive functions such as visual memory, attention, flexible thinking, and planning are found to be correlated with emotion recognition.

Reliability and Validity of Rowland Universal Dementia Assessment Scale in Turkish Population.

BACKGROUND: The aim is to validate Turkish version Rowland Universal Dementia Assessment Scale (RUDAS). METHODS: One hundred forty patients (>65 years) were included. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition -V was used in all patients. Rowland Universal Dementia Assessment Scale was applied for 2 days. Results were compared with Mini-Mental State Examination; reliability, validity, and statistical values were determined. RESULTS: Time validity was verified. Mini-mental state examination was correlated 45.3% in control and 73% in dementia group. Factor weights varied between 0.44 and 0.81; factor construct was verified as 6-item scoring. When 25 was cutoff point, sensitivity was 92.86% and specificity was 92.86%. Content validity index was found to be 100% by 7 specialists. Cronbach α (0.692) and test-retest reliability (intraclass correlation = 0.987) were determined. CONCLUSION: Rowland Universal Dementia Assessment Scale (Turkish) is validated and verified as reliable. Test could be applied for 5 minutes approximately; results are not affected by educational status, immigrant status, and language used; however, age and gender have significant effect on results.

Impulse control disorders in patients with prolactinoma receiving dopamine agonist therapy: a prospective study with 1 year follow-up.

OBJECTIVE: To assess prospectively the prevalence of impulse control disorders (ICD), psychiatric symptoms, and their clinical correlates in patients with prolactinoma receiving dopamine agonists (DA) in comparison to those with non-functioning pituitary adenomas (NFA) and healthy controls (HC). METHODS: A total of 25 patients with prolactinoma, 31 with NFA, and 32 HCs were included in the study. All patients and controls were screened for the presence of ICDs and other psychiatric disorders using revised version of Minnesota Impulsive Disorders Interview (MIDI-R), Barratt Impulsiveness Scale (BIS-11), Symptom Check List (SCL-90-R) questionnaire and Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: We detected two new cases (8%) of ICD associated with DAs. Both cases presented with hypersexuality, which reversed totally or decreased upon discontinuation of the drug. The re-challenge of the DA in a smaller dose has led to either no symptoms or weaker symptoms than before. There was an increase in the number of patients who screened positive on obsession, interpersonal sensitivity, paranoid ideation, and additional items subscales of SCL-90-R in comparison to HCs at the end of the study period (p < 0.05 for all). Likewise, cumulative DA dose was positively correlated to obsession, interpersonal sensitivity, paranoid ideation, hostility, phobic anxiety subscales, and GSI scores of SCL-90-R (p < 0.05 for all). CONCLUSIONS: DAs are associated with a small but substantial short-term risk of ICD development and a broad range of psychiatric symptoms in patients with prolactinoma receiving DAs.

Evaluation of the Relationship Between Attention Deficit Hyperactivity Disorder Symptoms and Chronotype.

INTRODUCTION: The aim of the study is to investigate the relationship between circadian characteristics and behavioral problems in children with Attention Deficit Hyperactivity Disorder (ADHD) (n=53), and to compare this group with healthy controls (n=38). METHOD: Fifty-three medication-free children with ADHD, aged 6-12 years, and 38 healthy children, age and sex matched, participated. Parents completed the Conners' Parent Rating Scale-Revised, the Children's Chronotype Questionnaire (CCTQ), and the Children's Sleep Habits Questionnaire (CSHQ) to assess sleep variables. RESULTS: ADHD children had more sleep-onset problems and parasomnias (in CSHQ) compared to healthy controls. However, circadian preferences did not differ between the groups in CCTQ scores. Another important finding was a mild correlation between parasomnia, bedtime on schooldays, and ADHD symptoms. CONCLUSION: Our study showed that children with ADHD showed more resistance to going to bed than did controls on school days. However, in contrast to our hypothesis, morningness/eveningness preference did not differ from controls in ADHD children.

Brainstem reflexes are hyperactive in patients with drug-induced akathisia.

Akathisia is a sensori-motor phenomenon which is generally encountered as an adverse effect of antidopaminergic medications suggesting involvement of dopaminergic pathways. We recently showed nociceptive flexor reflex was altered in akathisia as compared to restless legs syndrome and therefore, these findings may indicate co-involvement of pathways other than dopaminergic ones. To examine functional status of different pathways, we investigated auditory startle reflex (ASR), startle response to somatosensory input (SSS), and trigemino-cervical reflex (TCR) in a group of patients with akathisia. Consecutive seven patients with drug-induced akathisia and age- and gender-matched healthy subjects were prospectively included in the study. The diagnosis was made by appropriate clinical criteria. Brainstem reflexes, ASR, SSS, and TCR were examined in all participants. The probability, onset latency, amplitude, and duration were measured and compared between groups. The probability and amplitudes of ASRs were significantly increased and durations of ASRs and TCRs were prolonged in the patient group. Latencies of all responses as well as patterns of startle responses were similar between groups. The results reveal hyperactivity of the ASR and TCR in drug-induced akathisia. Hyperactive ASRs and TCRs also confirm suprasegmental hypodopaminergic state in akathisia. Although we keep in mind the confounding effects due to concurrent antidopaminergic treatments and the small sample group, we speculate that hyperactive ASRs and TCRs might be related to deficient control by forebrain and limbic-mainly amygdala-network in patients with drug-induced akathisia.

Lower limb flexor reflex: Comparisons between drug-induced akathisia and restless legs syndrome.

BACKGROUND AND OBJECTIVE: Akathisia is characterized by restlessness and crawling sensations similar to restless legs syndrome (RLS). Long latency flexor reflex (LLFR) which has helped to advance RLS pathophysiology has never been investigated in akathisia. Due to the clinical commonalities of akathisia and RLS, we investigated the behavior of LLFR in patients with akathisia aiming to understand pathophysiology of akathisia. PATIENTS AND METHODS: Seven patients with neuroleptic-induced akathisia, 12 drug-naïve patients with primary RLS and 17 healthy subjects were prospectively enrolled in the study. LLFR was recorded from unilateral tibialis anterior (TA) and long head of biceps femoris (BF) muscles after stimulating the sole by trains of electrical stimuli. We measured amplitude, latency, duration, presence of response and compared between three groups. RESULTS: One-way ANOVA showed mean durations of early and late responses recorded over TA were the longest in akathisia group compared to both RLS group and healthy subjects (p=0.012). The spatial spread of LLFR in akathisia patients was comparable to those of healthy subjects whereas presence of response on BF was significantly less in akathisia than RLS group. CONCLUSIONS: Our findings indicate increased excitability of LLFR pathway in akathisia group. These findings are probably due to lack of inhibition originated in regions other than those known to downregulate in RLS.