Investigation of endophenotype potential of decreased fractional anisotropy in pediatric bipolar disorder patients and unrelated offspring of bipolar disorder patients.

BACKGROUND: Bipolar disorder (BD) is a severe psychiatric disorder associated with structural and functional brain abnormalities, some of which have been found in unaffected relatives as well. In this study, we examined the potential role of decreased fractional anisotropy (FA) as a BD endophenotype, in adolescents at high risk for BD. METHODS: We included 15 offspring of patients with BD, 16 pediatric BD patients, and 16 matched controls. Diffusion weighted scans were obtained on a 3T scanner using an echo-planar sequence. Scans were segmented using FreeSurfer. RESULTS: Our results showed significantly decreased FA in six brain areas of offspring group; left superior temporal gyrus (LSTG; P < .0001), left transverse temporal gyrus (LTTG; P = .002), left banks of the superior temporal sulcus (LBSTS; P = .002), left anterior cingulum (LAC; P = .003), right temporal pole (RTP; P = .004) and left frontal pole (LFP; P = .017). On analysis, LSTG, LAC, and RTP demonstrated a potential to be an endophenotype when comparing all three groups. FA values in three regions, LBSTS, LTTG, and LFP were increased only in controls. CONCLUSION: Our findings point at decreased FA as a possible endophenotype for BD, as they were found in children of patients with BD. Most of these areas were previously found to have morphological and functional changes in adult and pediatric BD, and are thought to play important roles in affected domains of functioning. Prospective follow up studies should be performed to detect reliability of decreased FA as an endophenotype and effects of treatment on FA.

Long-acting injectable antipsychotics for prevention and management of violent behaviour in psychotic patients.

BACKGROUND AND AIMS: It has been well established that long-term antipsychotic treatment prevents relapse, lowers number of rehospitalisations, and also effectively reduces violent behaviour. Although violent behaviour is not a typical manifestation of schizophrenia or other psychotic disorders, the diagnosis of psychosis increases the overall risk of violence. One of the few modifiable factors of violence risk is adherence with medication. In contrast, non-adherence with drug treatment and subsequent relapse increases risk of violent acts. Non-adherence can be addressed partially by long-acting injectable antipsychotics (LAI). The aim of our review was to examine the role of antipsychotic drugs, especially LAI, in prevention and management of violent behaviour in psychosis. METHODS: This is a non-systematic, narrative review of the data from open, naturalistic, retrospective, and population studies, case series, and post hoc analyses of randomised controlled trials. Search of electronic databases (PubMed, Embase) was performed to identify relevant papers. RESULTS: Nine published papers (3 cross-sectional chart reviews, 4 retrospective studies, 2 prospective, randomised trials) were found. The results indicated positive clinical and antiaggressive effects of LAI in psychotic patients with high risk of violent behaviour. DISCUSSION: Reviewed evidence suggests that secured drug treatment with LAI may have clinical benefit in schizophrenia patients with high risk of violent behaviour. LAI significantly reduced the severity of hostility, aggressivity, number of violent incidents, and criminal offences. These findings are supported further by the empirical evidence from clinical practice, high rates of prescribed LAI to schizophrenia patients in high-security and forensic psychiatric facilities. CONCLUSIONS: Available data encourage the use of LAI in forensic psychiatry, especially during court-ordered commitment treatment.

[Time profile of serum THC levels in occasional and chronic marihuana smokers after acute drog use - implication for drivind motor vehicles]. / Casový profil hladin THC v krevním séru u rekreacních a chronických kuráku marihuany po akutním uzití drogy - implikace pro rízení motorových vozidel.

Cannabis consumption has individual influence to cognitive and psychomotor functions of drivers and it has been generally accepted that driving under influence is risky in the perspective of traffic safety. However, rules how to assess fitness to drive are not quite clear. The psychoactive compound delta-9-tetrahydrocannabinol (THC) impairs cognition, psychomotor behaviour and driving performance in a dose-related manner approximately. After a single drug dose, THC blood concentration peaks within minutes, before the end of smoking, with a subsequent rapid decrease to the analytical limit of detection. Peak euphoria is delayed compared to THC peak blood concentration and physiological and behavioural effects return to baseline within 3-5 hours. In chronic users, the lipophilic THC accumulates in fat tissues, where its slow redistribution into blood is the rate limiting process in its terminal elimination. In our experimental study we have attempted to contribute to this discussion with results obtained from human volunteers - cannabis consumers in Czech Republic. Aim of our study was to document the time profile of serum THC level in occasional and chronic cannabis users. The observational interval covered the time immediately after the drug consumption (an own cigarette/joint) till 24 hours after. Our preliminary results have shown that in occasional users, THC serum levels cannot be detected already 4 hours after usual cannabis dose, whereas in chronic users measurable THC concentrations in serum persist longer. Moreover, some chronic consumers were practically with permanent THC detection during our observation period and also the chronic users consumed higher THC doses significantly related to doses in occasional ones. Presented results of the experimental study with human volunteers confirm a great individual variability of the kinetic profile of THC in blood due to complicated redistribution. The practical forensic question is how long the psychotropic effects of THC can persist after the last drug dose. In chronic users there are well documented indications of long term adverse effects to neurocognitive functions. THC blood level itself can not directly document the intensity of impairment of a driver. Moreover, the concentration of THC in blood at the time of driving is probably substantially higher than at the time of blood sampling. Therefore due to the prevention of traffic risk, some countries adopted per se traffic legislation based on analytical principle with minimum tolerance to illegal drugs in blood of drivers at driving. Low blood concentrations of THC close to the limit of detection of a specific toxicological method (GC-MS or LC-MS) are justified in an effective traffic legislation.

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. METHODS: Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. RESULTS: Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. CONCLUSIONS: Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

Altered Neural Correlate of the Self-Agency Experience in First-Episode Schizophrenia-Spectrum Patients: An fMRI Study.

BACKGROUND: The phenomenology of the clinical symptoms indicates that disturbance of the sense of self be a core marker of schizophrenia. AIMS: To compare neural activity related to the self/other-agency judgment in patients with first-episode schizophrenia-spectrum disorders (FES, n = 35) and healthy controls (HC, n = 35). METHOD: A functional magnetic resonance imaging (fMRI) using motor task with temporal distortion of the visual feedback was employed. A task-related functional connectivity was analyzed with the use of independent component analysis (ICA). RESULTS: (1) During self-agency experience, FES showed a deficit in cortical activation in medial frontal gyrus (BA 10) and posterior cingulate gyrus, (BA 31; P < .05, Family-Wise Error [FWE] corrected). (2) Pooled-sample task-related ICA revealed that the self/other-agency judgment was dependent upon anti-correlated default mode and central-executive networks (DMN/CEN) dynamic switching. This antagonistic mechanism was substantially impaired in FES during the task. DISCUSSION: During self-agency experience, FES demonstrate deficit in engagement of cortical midline structures along with substantial attenuation of anti-correlated DMN/CEN activity underlying normal self/other-agency discriminative processes.

Social and functional capacity of schizophrenia patients: A cross-sectional study.

BACKGROUND: The chronic course of schizophrenia typically results in severe social, vocational and functional impairment, interferes with patients' autonomy, reduces quality of life and increases disability. AIMS: The aim of our study was: (1) to assess social and functional impairment in schizophrenia outpatients from the Czech Republic and Slovakia; and (2) to examine a relationship between functioning and antipsychotic treatment and demographic variables. METHODS: Schizophrenia outpatients in a stable phase of illness, treated with current antipsychotic medication for a minimum of one month, were enrolled for the study. Demographic and medication data were recorded. The Personal and Social Performance (PSP), Subjective Well-Being under Neuroleptics (SWN) and Clinical Global Impressions (CGI) scales were administered. RESULTS: The total number of study subjects was 926. Most PSP values were within the interval of moderate impairment. Functional performance correlated positively with subjective satisfaction with medication and negatively with symptom severity. Higher education predicted better functioning on PSP. The best performance was associated with a stable relationship and a useful work role. Patients who showed the best level of functioning were more likely to be treated with antipsychotic monotherapy. No difference among drugs in monotherapy was found in subjective satisfaction. CONCLUSIONS: The PSP values of stable schizophrenia outpatients indicated a moderate degree of impairment. Improvement of functional capacity remains one of the unmet needs of schizophrenia patients.