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Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
Aims
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
Method
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
Conclusions
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalised patients is critical as the pandemic progresses. This observational cohort study aimed to characterise the independent associations between the clinical outcomes of hospitalised patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, UK between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling. The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Scale <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality. These important data will aid clinical risk stratification and provide direction for further research.
To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.
Design:
Case–control study.
Setting:
We collected data from international participants via an online survey.
Participants:
In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.
Methods:
Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.
Results:
HCP infection was associated with non–aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04–1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1–16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2–0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4–0.7).
Conclusions:
COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients has been associated with a more rapid decline in lung function, increased hospitalisation and mortality. The aim of this study was to evaluate the clonal relationships among 116 MRSA isolates from 12 chronically colonised CF pediatric patients over a 6-year period in a Rio de Janeiro CF specialist centre. Isolates were characterised by antimicrobial resistance, SCCmec type, presence of Panton-Valentine Leukocidin (PVL) genes and grouped according to DNA macrorestriction profile by pulsed-field gel electrophoresis (PFGE) and spa gene type. High resistance rates were detected for erythromycin (78%) and ciprofloxacin (50%) and SCCmec IV was the most common type (72.4%). Only 8.6% of isolates were PVL positive. High genetic diversity was evident by PFGE (39 pulsotypes) and of nine that were identified spa types, t002 (53.1%) and t539 (14.8%) were the most prevalent. We conclude that the observed homogeneity of spa types within patients over the study period demonstrates the persistence of such strain lineages throughout the course of chronic lung infection.
Le parcours de soins des patients atteints de TDA/H est mal connu. Cette enquête nationale a pour objectif de préciser les étapes d’évaluation successives menant au diagnostic ainsi qu’au traitement du TDA/H et d’identifier des éléments susceptibles d’être améliorés.
Méthode
Enquête transversale menée en France du 04/11/2013 au 31/01/2014 auprès d’un échantillon national de 61 médecins prenant en charge des enfants atteints de TDA/H, à l’aide d’un auto-questionnaire remis aux patients/parents.
Résultats
Quatre cent soixante-treize questionnaires analysés. Les premiers signes (troubles du comportement [78,2 %] et de l’attention [70 %]) sont repérés vers 4,5 ans, principalement hors du milieu familial. Le diagnostic est posé à l’âge de 8,1 ans, environ 4 ans après l’observation des premiers signes. Les familles consultent en moyenne 3,5 professionnels de santé avant que le diagnostic ne soit évoqué. Le psychiatre/pédopsychiatre est le plus consulté quelle que soit l’étape d’évaluation. Lors de la 1re étape, seuls 10,7 % des patients sont diagnostiqués. Ce délai pourrait en partie expliquer les taux élevés de redoublement (31,5 %), notamment en CP et CE1, et d’insatisfaction vis-à-vis de la prise en charge, principalement lors de la 1re étape d’évaluation (38,6 % d’insatisfaits). Deux groupes de patients ont été mis en évidence par une analyse en cluster : le premier (89,9 % de garçons) présente des problèmes de comportement, d’agitation, et des difficultés familiales ; le 2e (49 % de garçons), dont l’hyperactivité est moins prononcée, a mis une année supplémentaire pour recevoir un diagnostic de TDA/H. Dans cet échantillon, plus de 2/3 des patients bénéficient d’un traitement médicamenteux, du méthylphénidate dans 98 % des cas. Le diagnostic tardif a été la principale source de préoccupation des proches.
Conclusion
Le délai d’environ 4 ans, des premiers signes au diagnostic, pourrait constituer une perte de chance pour les enfants atteints de TDA/H.
Life expectancy in schizophrenia is shortened, 15 years to 32 years. Increased cardiovascular morbidity is thought to have a major contribution.
Methods
A nurse practitioner was appointed for metabolic screening. The cut-off points were according to the NCEP 2005 criteria, except for glucose (cut-off: 6,0 mmol/l).
All outpatients in two FACT teams in Alkmaar were asked to participate in the measurement of the metabolic syndrome. Blood pressure was twice measured at two different visits, that took place 4 weeks apart. If laboratory result was abnormal, the measurement was repeated.
Results
Out of the 204 patients in outpatient care who were asked, 67 refused participation. All in all, 137 patients participated, 91 male (46,3 years (SD: 12,2) and 46 female (51,7 yrs; SD: 11,6) patients. The vast majority (N=126 (92,6%) were Caucasian. Obesity was present in 32% of the male and 48% of the female patients compared to 16% in the general population. Normoglycemia was established in only 72,2% of the population compared to 95% in the same aged general population. Repeated hyperglycemia was present in 24,1% of the population.
Conclusion
In 137 patients with severe mental illness, mean age 48 years, we found that
1. obesity was twice as prevalent as in the patient population.
2. using the conservative NECP 2001 criterion for hyperglycemia, one out of four patients had a confirmed pre-diabetic hyperglycemia.
Intensive screening, therapy and preferably prevention are advised and needed to prevent major medical costs and massive medial consumption in this high-risk population.
People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension, and dyslipidaemia.
Over recent years both national and international groups have developed screening and monitoring guidelines but these are not being routinely implemented in the clinical care of patients. A review of the literature identifies barriers to comprehensive screening, monitoring and treatment of somatic co-morbidities on the level of professionals (both within psychiatry as well as in primary care), patients, health care systems (organisational and financial aspects) and health policies.
Psychiatrists and primary care physicians should play an active role in ensuring that patients with mental illness are not disadvantaged. Measures should include the assessment and management of cardiovascular risk factors and diabetes as part of the care of their psychiatric patients. When indicated, shared care with cardiologists, diabetologists, specialist nurses or other specialists should be established.
The aim of the recent joint statement on cardiovascular disease an diabetes in people with severe mental illness of the EPA, EASD and ESC is to reduce cardiovascular risk and to improve diabetes care in patients with SMI and to improve overall health and well-being of the patients (De Hert et al. 2009). This should reduce the burden of physical illness for patients, their families and healthcare services.
Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still frequent. The aim of this paper was to perform a systematic review and critically evaluate the literature on cardiometabolic and endocrine side-effects of SGA in children and adolescents through a Medline/Pubmed/Google Scholar search of randomized, placebo controlled trials of antipsychotics in children and adolescents (<18 years old) until February 2010. In total, 31 randomized, controlled studies including 3595 paediatric patients were identified. A review of these data confirmed that SGA are associated with relevant cardiometabolic and endocrine side-effects, and that children and adolescents have a high liability to experience antipsychotic induced hyperprolactinaemia, weight gain and associated metabolic disturbances. Only weight change data were sufficiently reported to conduct a formal meta-analysis. In 24 trials of 3048 paediatric patients with varying ages and diagnoses, ziprasidone was associated with the lowest weight gain (−0.04 kg, 95% confidence interval [CI]: −0.38 to +0.30), followed by aripiprazole (0.79 kg, 95% CI: 0.54 to 1.04], quetiapine (1.43 kg, 95% CI: 1.17 to 1.69) and risperidone (1.76 kg, 95% CI: 1.27 to 2.25) were intermediate, and olanzapine was associated with weight gain the most (3.45 kg, 95% CI: 2.93 to 3.97). Significant weight gain appeared to be more prevalent in patients with autistic disorder who were also younger and likely less exposed to antipsychotics previously. These data clearly suggest that close screening and monitoring of metabolic side effects is warranted and that the least cardiometabolically problematic agents should be used first whenever possible. A good collaboration between child- and adolescent psychiatrists, general practitioners and paediatricians is essential to maximize overall outcomes and to reduce the likelihood of premature cardiovascular morbidity and mortality.
Study of risk factors of diabetes mellitus from the general population in a schizophrenic population.
Method:
Measurement of glucose and insuline levels, fasting and 120’ after oral glucose tolerance test (OGTT) and calculating of HOMA-IR and HOMA-B.
Results:
We studied 167 outpatients, mean age 40.2 years, 90.9% Caucasian, suffering from schizophrenia (83%) or schizoaffective disorder (17%).
Age could not be confirmed as a risk factor on any of the glucose or insuline measurements or HOMA in patients with typical or atypical antipsychotics.
With bodyweight, patients with typical differed from those with atypical antipsychotics. Weight was not a risk factor on any measurement or model in with typical antipsychotics. In patients with atypical, a significant correlation with levels of plasma glucose (p=0.017), insuline (p= 0.003 resp. p= 0.010) or glucose homeostasis models (p= 0.004 resp. p= 0.016). Fasting plasma glucose (FPG) was the notable exception (p=0.987).
Conclusion:
Diabetes risk factors age and weight behave differently in schizophrenia or schizoaffective disorder.
The finding that age was not a risk factor, suggests that age is not a suitable criterion for the decision of glucose screening in this population.
The different effect of weight (a risk factor only in patients treated with atypical, but not with typical antipsychotics) suggests in different pathophysiological pathway.
As FPG was the only measurement with no correlation with either risk factors, this suggests that FPG is insufficiently sensitive for detection of disturbed glucosemetabolism in schizophrenia. Additional measurements (fasting insuline, HOMA-IR, HOMA-B, OGTT) seem to be necessary.
Given the limited knowledge on the long-term outcome of adolescents who receive electroconvulsive therapy (ECT), the study aimed to follow-up adolescents treated with ECT for severe mood disorder. Eleven subjects treated during adolescence with bilateral ECT for psychotic depression (n = 6) or mania (n = 5), and ten psychiatric controls matched for sex, age, school level, and clinical diagnosis, completed at least 1 year after treatment a clinical and social evaluation. Mean duration between time of index episode and time of follow-up evaluation was 5.2 years (range 2–9 years). At follow-up: (1) all patients except two in the control group received a diagnosis of bipolar disorder. (2) Fifteen patients had had more than one episode of mood disorder. (3) The two groups did not differ in social functioning nor school achievement. (4) Impact on school achievement was related to the severity of the mood disorder rather than ECT treatment. The results suggest that adolescents given ECT for bipolar disorder, depressed or manic, do not differ in subsequent school and social functioning from carefully matched controls.
Catatonia is a well-defined motor syndrome. Its prevalence has been found between 9.5 and 13.6% in various emergency psychiatric units.
Methods:
A prospective evaluation was conducted for every patient admitted in the psychiatric emergency facility of the police authority in Paris (Infirmerie Psychiatrique près la Préfecture de Police) during 30 days. Catatonic symptoms were collected, as well as other clinical variables, by using a check-list adapted from DSM-IV criteria.
Statistical analysis:
Catatonic and non catatonic patients were compared using khi2 for categorical variables and ANOVA for continuous variables. Variables which were statistically different between the two groups were entered in a step-wise logistic regression model (level of entry: .05).
Results:
The number of patients included was 229. A full catatonic syndrome (i.e. at least two prominent catatonic symptoms lasting for at least 24 hours) was found in 30 patients (13.1%). Main diagnoses in these patients were: schizophrenic disorders (24), bipolar disorders (4) and acute alcohol/street drugs intoxications (2). Ten out of 30 catatonic patients were not meeting anymore the diagnostic criteria for a catatonic syndrome at the end of the 24-48 hours observation and treatment time. Clinical characteristics of patients who were catatonic at entry, and those of patients who remained catatonic at the end of their admission are described and discussed.
Conclusion:
Catatonia was frequent (13.1%), and 8.7% of the sample still presented a catatonic syndrome at the end of 24-48 hours of treatment.
To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD).
Methods:
Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300 mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150 mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed.
Results:
One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks.
Conclusions:
Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.
To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children.
Method
A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners’ parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring.
Results
The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated.
Conclusions
The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.
Itzhaky (2012) found significantly lower vitamin D level in patients with schizophrenia than in healthy controls.
Objective
Measurement of vitamine-D in bipolar and schizophrenia/schizoaffective outpatients.
Aims
Determining the prevalence of vitamin D deficiency in outpatients with bipolar disorder, schizophrenia or schizoaffective disorder in the Netherlands.
Method
Outpatients in the Alkmaar region aged 18w65 years with a bipolar disorder, Schizophrenia/schizoaffective disorder were asked to add vitamin D levels determination to the annual standard blood sample taking.
Results
111 patients, 54 with schizophrenia/schizoaffective disorder and 57 with bipolar disorder, participated. 58 (53%) was male, mean age 47 (SD 9.9) years. 64 (58%) showed vitamin-D insufficiency (< 50 nmol/L), 32 (29%) vitamin-D deficiency (< 30 nmol/L). 7 (6.3%) female patients aged >50 had a serum level between 30–50 nmol/l. No significant differences were found between bipolar disorder and schizophrenia/schizoaffective disorder.
Conclusion
To prevent osteoporosis, vitamin D supplementation is advised with vitamin D-levels below 30nmol/l or below 50 in women >50 years and men >70 years, (Dutch Health Council). Using to this criterion 39 patients (35%) of the study-population needed vitamine-D supplement. If confirmed, addition of vitamine-D levels to the annual somatic screening of patients with bipolar disorder, schizophrenia/schizoaffective disorder is indicated. Limitation: the impact of the season on vitamine-D levels was not corrected for in either population.
The purpose of this talk is to present a study on risk assessments of female sex offenders. The literature on this issue focuses mainly on male sex offenders. By contrast, the literature on female sex offenders is scarce and mostly recent. Moreover, the law regarding sex offenders does not usually deal with offences committed by females. For example, in Israel section 345 of the criminal code refers solely to male rapists. In recent years we are witnessing a rise in the number females who are brought to justice for committing sex offences. Sex offence assessment is a professional process whereby the probability that a certain behavior will occur within certain terms and in a given range of time is assessed. The assessment takes into account the attributes of both, the assault and the perpetrator. During the last few years much research on risk assessment of male sex offenders has been carried out. However, research on female sex offenders is scanty. As of today, there is no theoretical or data base for assessing sexual recidivism of female sex offenders. Assessment criteria are still unclear, and it is still impossible to ascertain whether the actuarial tools which are commonly used for risk assessment of male sexual offenders are valid for females. In the present study actuarial tools and clinical criteria for assessing female sex offenders were compared. The main finding we found is correlation between actuarial tools and dynamic criteria. The main criticism is that the actuarial tools includes
Reduced life expectancy is one of the main concerns in the treatment of schizophrenia. The size of reduction is a consistent phenomenon in studies across the oceans. It varies from 16–32 years (USA, Colton & Manderscheid 2006), 22–25 years (Finland, Tiihonen 2009) and 15–20 years (Nordic European countries, Wahlbeck 2011). Increased prevalence of cardiovascular risk factors has been shown to contribute significantly to increased mortality in schizophrenia (Osby 2001). Diabetes mellitus, a major age dependent cardiovascular risk factors, has been found to be ten times as prevalent in the relative young age between 30–39 years (Cohen 2006).
Hundred years ago Kraepelin coined the diagnostic entity ‘dementia praecox’ for what is currently called schizophrenia. In parallel we hypothesized a somatic process - with the provisional name of ‘premature ageing’ - to occur that would explain both these two phenomena at once, the increased prevalence of the age dependent disease diabetes and the premature death in schizophrenia. Advanced glycated endproducts (AGEs), endproducts of the metabolisation of glucose, have been shown, in the general Dutch population, to increase age-dependently (Koetsier 2010). We hypothesized the concentration of AGEs in schizophrenia tocorrespond that found in 20 years older general population. We present the results of the measurements in the first fifty patients.
The consequence fo the finding could be twofold. First theorethically, a confirmation of the concept premature ageing. Second a rpactical issue, that patients with schizophrenia should be considered and treated not according to their calendar age but to according to their biological age.
Despite its high prevalence, the validated treatment for ADHD is chronic administration of psychostimulants, which is associated with side effects and occasionally not tolerated. Deep TMS using special coil designs for targeting neural networks linked with neuropsychiatric disorders, may become a viable alternative.
Objectives
Comparison of rTMS treatment using deep, figure-8 and sham coils on ADHD symptoms.
Methods
In the current randomized, sham-controlled study, adult ADHD patients received 15 daily sessions of high-frequency rTMS directed to the right prefrontal cortex (rPFC), using either deep, figure-8, or a sham coil. ADHD symptoms and cognitive alterations were assessed using the CAARS-INV, self–report questionnaires and performance tests. Additionally, the stop signal task (SST) combined with EEG measures was used to asses behavioural inhibition and ERPs. EEG responses to an inhibitory protocol of paired TMS pulses over the rPFC were measured before and after treatments. A healthy control group was evaluated at baseline for comparison.
Results
Several ADHD symptoms were improved in patients that received dTMS but not standard figure-8 or sham treatment (p=0.007, CAARS; p=0.014, SST). Differences between ADHD patients and healthy controls were demonstrated in ERPs during the SST, and in response to single and paired TMS pulses. The lower amplitudes of ERPs in patients correlated with ADHD symptoms and behavioural inhibition measures.
Conclusions
Repeated stimulation of deep areas in the rPFC has therapeutic potential, where rPFC excitability is impaired in ADHD patients. Ongoing analysis attempts to establish the neurophysiological measures as predictors and biomarkers for effectiveness of dTMS treatment.
White matter development during adolescents is crucial for a mature integration of neural networks in the brain. Autism spectrum condition (ASC), characterized by social and communication difficulties and rigid behaviour may interact with white matter development observed during adolescence. Changes in white matter development may link autistic symptoms to its genetic underpinnings and explain a 10-fold increase in susceptibility to ASC among siblings of individuals with ASC.
We used diffusion tensor imaging to study an association between age and white matter integrity measures, fractional anisotropy (FA) and mean diffusivity (MD), in adolescents with ASC, their siblings and age-matched healthy controls. Diffusion-weighted data were acquired with 64-direction protocol with 3mm slices and TR of 6600ms and tract-based spatial statistics analysis was performed.
The control subjects showed robust signs of increase in white matter integrity correlated with age. In contrast, individuals with ASC showed significantly lower negative correlation between MD and age in a broad area centred in the right superior longitudinal fasciculus (rSLF). When the three eigenvalues constituting a tensor ellipsoid were considered separately, siblings of individuals with ASC showed a diminished negative correlation between the second eigenvalue and age also centred in the rSLF.
Adolescents with ASC and their siblings experience alterations in white matter development in comparison to age-matched healthy controls, which are similar in direction yet different in scale for the two affected groups. The alterations are observed in the area associated with flexibility of behaviour and may explain both symptoms of ASC and increased susceptibility to ASC.