Potential of Extracellular Vesicles in Neurodegenerative Diseases: Diagnostic and Therapeutic Indications.

Extracellular vesicles (EVs) are membrane-bound vesicles, including exosomes and microvesicles. EVs are nanometer sized, found in physiological fluids such as urine, blood, cerebro-spinal fluid (CSF), with a capacity of transferring various biological materials such as microRNAs, proteins, and lipids among cells without direct cell-to-cell contact. Many cells in the nervous system have been shown to release EVs. These vesicles are involved in intercellular communication and a variety of biological processes such as modulation of immune response, signal transduction, and transport of genetic materials with low immunogenicity; therefore, they have also been recently investigated for the delivery of therapeutic molecules such as siRNAs and drugs in the treatment of diseases. In addition, since EV components reflect the physiological status of the cells and tissues producing them, they can be utilized as biomarkers for early detection of various diseases. In this review, we summarize EV application, in diagnosis as biomarker sources and as a carrier tool for drug delivery in EV-based therapies in neurodegenerative diseases.

Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker.

OBJECTIVES: Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association - across the brain and cervical spinal cord - between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). METHODS: Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. RESULTS: Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (- 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: - 11%, p = 0.01; spine: - 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). INTERPRETATION: In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability.

Training health professionals to conduct family education for families of patients with first-episode psychosis: adherence to protocol.

OBJECTIVE: The implementation of family psychoeducation at the service delivery level is not without difficulty. Few mental health professionals receive special training to work with families especially in Iran. The aim of the present study was to evaluate the effectiveness of training health professionals in terms of their adherence to protocol. METHOD: Eight professionals (general practitioners, nurses and social workers) participated in a training program for health professionals as part of the Roozbeh First-Episode Psychosis Program (RooF) to conduct family psychoeducation. Training included a 3-day- workshop and 12 supervision sessions during the course of the implementation of the psychoeducation program. The family psychoeducation sessions (multiple-family group or single-family home-based) were tape-recorded. Transcripts of the audiotaped sessions were analyzed based on the content of the manual and were scored accordingly. RESULTS: Twenty-four recorded sessions were analyzed in terms of the adherence to protocol, the number of questions and the time for each session. The overall rating showed a 72% adherence to the protocol. Multiple-family group sessions had a higher rate compared to the single-family home-based family psychoeducation sessions (79% to 69%) as well as the time spent and questions asked. The rate of adherence to the protocol of conducting the family psychoeducation sessions had not changed over time. CONCLUSION: Considering the amount of time taken for training and supervision, the level of adherence to the protocol was satisfactory. Tape recording sessions and regular supervision would be beneficial following specialized training. Further research is needed to tailor the amount of training and supervision required for professionals to conduct family psychoeducation programs in different settings.

Executive dysfunction in treated phenylketonuric patients.

OBJECTIVES: Executive function deficits have been described in early and continuously treated patients with phenylketonuria (PKU). The aim of this study was to examine performance on executive function tasks of treated patients with PKU diagnosed by 2 years of age. PATIENTS AND METHODS: Ten patients with PKU and normal intelligence score who were diagnosed before the age of 2 years and subsequently treated continuously, were compared with 15 typically developing control children on a battery of neuropsychological tests, including the tower of London (TOL), continuous performance test (CPT), and Stroop test. RESULTS: PKU cases showed significantly poorer performance on the TOL task compared to the control group with the difference being significant in the first three levels of the test. With the CPT, PKU cases had significantly more omission errors than control subjects. On the Stroop test there was no statistically significant difference between the groups. No significant correlation was found between the concurrent serum phenylalanine (Phe) level and results of the executive tests in PKU patients. CONCLUSION: This study identified executive dysfunction in early-treated PKU patients with normal IQ, particularly in the planning and attention domains. Further studies are required to compare the results with those from other neurodevelopmental disorders such as ADHD and autism, to establish whether the pattern of findings is specific to PKU.

A Persian translation of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: psychometric properties.

OBJECTIVE: The aim of this study is to assess the reliability and validity of a Persian translation of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders (SCID-I) through a multicenter study in a clinical population in Iran. METHOD: The sample consisted of 299 subjects admitted to outpatient or inpatient services of 3 psychiatric centers in Tehran, Iran. The SCID was administered by trained interviewers. To study the test-retest reliability, a second independent SCID interview was administered to 104 of the entire sample within 3 to 7 days of the first interviews. For the assessment of validity, the SCID diagnoses were compared with the consensus clinical diagnoses made by 2 psychiatrists for all 299 patients. RESULTS: Diagnostic agreements between test and retest SCID administration were fair to good for most diagnostic categories. Overall weighted kappa was 0.52 for current diagnoses and 0.55 for lifetime diagnoses. Specificity values for most psychiatric disorders were high (>0.85); the sensitivity values were somewhat lower. CONCLUSIONS: The Persian translation of the SCID yields diagnoses with acceptable to good reliability and validity in a clinical population in Iran. This supports the cross-cultural use of the instrument.

Duration of untreated psychosis and pathways to care in patients with first-episode psychosis in Iran.

AIM: This is the first study on the duration of untreated psychosis and pathways to care among patients with first-episode psychosis in Iran as a developing country. METHODS: Ninety-one patients with a first episode of non-organic psychosis admitted to a university-affiliated psychiatric hospital in Iran were assessed for duration of untreated psychosis (DUP), pathways to care and mode of onset. RESULTS: Median DUP was 11 weeks (mean = 52.3 weeks). Following the onset of psychosis, most patients were first seen by a psychiatrist (n = 23, 25.3%), a traditional healer (n = 21, 23.1%) or a general practitioner (n = 16, 17.6%). Most referrals to the psychiatric hospital were made by the family (n = 30, 33.1%), or health professionals (n = 29, 31.9%). Acute onset and rural place of residence were associated with shorter DUP in multivariate analysis. CONCLUSIONS: Median DUP was not long in an inpatient sample with first-episode psychosis, which may be due to the preponderance of affective and acute psychoses in this sample and some help-seeking or service variables.

Consanguineous Iranian kindreds with severe Tourette syndrome.

The search for vulnerability genes for Tourette syndrome has been ongoing for nearly three decades. The contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. Homozygosity mapping has been successfully used to detect recessive loci within populations with high rates of consanguinity. Using this technique, even quite small inbred families can be informative due to autozygosity in which the two alleles at an autosomal locus are identical by descent (i.e., copies of a single ancestral gene). To explore the utility of this approach, we identified 12 consanguineous Iranian families. Remarkably, these families were seen with an unusual natural history characterized by the early onset of vocal tics and coprolalia and frequent comorbidity with obsessive-compulsive disorder. Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder.

Acute treatment response and its predictors in patients with first-episode psychosis in Iran.

OBJECTIVE: The aim of this paper was to investigate the acute treatment response and its predictors in a sample of patients with first-episode psychosis admitted to a psychiatric hospital in Iran. METHOD: A total of 163 patients with first-episode psychosis were treated with antipsychotics and other medications as prescribed by their treating psychiatrists. Sociodemographic and premorbid data at baseline and clinical data at both baseline and discharge (6+/-1 weeks after admission) were collected. RESULTS: Patients showed a response rate of 71.4% for negative symptoms, 91.5% for positive symptoms and 67.5% for functioning. Those having a positive family history and less severe negative symptoms at baseline were less likely to respond in terms of negative symptoms. Higher premorbid and lower baseline functioning as well as acute onset were associated with the treatment response. CONCLUSIONS: Acute treatment response of first-episode psychosis in a clinical sample of a developing country seems to be higher than that of developed countries. However, predictors of response are comparable.