Shaping Future Doctors' Minds: Effects of Biological and Social Models on Medical Students' Views on Depression.

OBJECTIVE: The aim of this study was to explore how changes in biologically based narratives versus socially focused ones affect medical students' perceptions of causes, treatment strategies, and social distance towards patients and their beliefs that patients can improve. METHODS: The sample consisted of 1652 medical students of 18 to 32 years of age from the Faculty of Medicine at the University of Belgrade. Three text passages describing a female with standard symptoms of depression were randomly assigned. Within the text, additional information about different circumstances was included: information about personal problems (group S), family mental disorder history (group B), or both (group BS). RESULTS: Although family history of mental illness does not necessarily imply heredity, group B assumed a biological cause of depression to be more probable and identified medication prescription as a more effective treatment approach than the other groups did. Changes in views towards treatment strategies from the first year to later years were observed with the medical model becoming more dominant. CONCLUSIONS: The results of this study warn us of a tendency towards thinking less about social causes and more about medication prescription when an indication of biological causes is present. Implications for the medical education of future doctors and clinical practitioners are discussed.

Are there two different forms of functional dystonia? A multimodal brain structural MRI study.

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) - the typical fixed dystonia (FixFD) phenotype and the "mobile" dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels.

The cumulative effect of genetic polymorphisms on depression and brain structural integrity.

In major depressive disorder (MDD), the need to study multiple-gene effect on brain structure is emerging. Our aim was to assess the effect of accumulation of specific SERT, BDNF and COMT gene functional polymorphisms on brain structure in MDD patients. Seventy-seven MDD patients and 66 controls underwent a clinical assessment, genetic testing and MRI scan. Compared with controls, patients were more BDNF-Val homozygotes, COMT-Met carriers and SERT-L' carriers. Thus, subjects were split into three groups: 1. High-frequency susceptibility polymorphism group (hfSP, subjects with all three SPs); 2. Intermediate-frequency SP group (ifSP, two SPs); and 3. Low-frequency SP group (lfSP, one/none SP). Cortical thickness, volumetry of hippocampus, amygdala and subcortical structures, and white matter (WM) tract integrity were assessed. Compared to controls, hfSP patients showed thinning of the middle frontal cortex bilaterally, left frontal pole, and right lateral occipital cortex, and smaller hippocampal volume bilaterally; and both hfSP and lfSP patient groups showed thinning of the left inferior parietal cortex and reduced WM integrity of the corpus callosum. Compared to patients, hfSP controls showed greater integrity of the fronto-occipital cortices and corpus callosum. We showed that cortical prefrontal and occipital damage of MDD patients is modulated by the SP accumulation, while damage to the parietal cortex and corpus callosum seem to be independent of genetic accumulation. HfSP controls may experience protective mechanisms leading to a preserved integrity of critical cortical and WM regions. Investigating the effect of multiple genes is promising to understand the pathological mechanisms underlying MDD. Hum Brain Mapp 37:2173-2184, 2016. © 2016 Wiley Periodicals, Inc.

Transcranial Sonography Characteristics of Cerebellar Neurodegenerative Ataxias.

Cerebellar neurodegenerative ataxias are a group of disorders affecting the cerebellum and its pathways with different neurological structures. Transcranial sonography (TCS) has been used for the evaluation of brain parenchymal structures in various diseases because of its fast and safe utilization, especially in neuropsychiatric and neurodegenerative diseases. The aim of our study was to investigate TCS characteristics of patients with neurodegenerative cerebellar ataxias. In our study, we included 74 patients with cerebellar degenerative ataxia; 36.5% had autosomal dominant onset, while 33.8% had sporadic onset. Standardized ultrasonographic planes were used for the identification of brain structures of interest. The SARA, INAS, neuropsychological and psychiatric scales were used for the further clinical evaluation of our study participants. The brainstem raphe was discontinued in 33.8% of the patients. The substantia nigra (SN) hyperechogenicity was identified in 79.7%. The third and fourth ventricle enlargement had 79.7% and 45.9% of patients, respectively. A positive and statistically significant correlation was found between SN hyperechogenicity with dystonia (p < 0.01), rigidity and dyskinesia (p < 0.05). The higher SARA total score is statistically significantly correlated with the larger diameter of the III (r = 0.373; p = 0.001) and IV ventricles (r = 0.324; p = 0.005). In such patients, the echogenicity of substantia nigra has been linked to extrapyramidal signs, and raphe discontinuity to depression. Furthermore, ataxia and its clinical subtypes have positively correlated with the IV ventricle diameter, indicating brain atrophy and brain mass reduction.

The Impact of Demographic and Clinical Factors on the Quality of Life in Patients with Neurodegenerative Cerebellar Ataxias.

In neurodegenerative cerebellar ataxias, not only ataxia but also extra-cerebellar signs have a significant impact on patients' health related to quality of life (HRQoL). The aim of this study was to evaluate the various aspects of HRQoL and predictors of QoL in patients with neurodegenerative cerebellar ataxias. We included a total of 107 patients with cerebellar degenerative ataxia. Patients filled out the validated Serbian version of the SF-36 used for the assessment of HRQoL. All patients were clinically evaluated using SARA, INAS, and neuropsychological tests to assess their global cognitive status and different psychiatric scales. The most frequent types of neurodegenerative cerebellar ataxias were autosomal dominant ataxias (38.3%) and sporadic ataxias (32.7%). Mean age at diagnosis was 35.3 ± 16.23 years, and disease duration was on average 12.1 ± 9.91 years. Mean total SF-36 score was 50.63 ± 20.50. Hierarchical regression analysis showed that in the case of the PHC score, the most significant predictors are the patient's actual age, severity of ataxia, and ACE total score. For MHC, the Hamilton depression score was the most important predictor. Our study has shown that HRQoL measured by SF-36 in patients with neurodegenerative cerebellar disorders is strongly influenced by impaired mobility and depression.

Social Cognition in Patients With Cerebellar Neurodegenerative Disorders.

OBJECTIVE: Cerebellar neurodegenerative disorders (CDs) are a heterogeneous group of disorders. It is known that the cerebellum plays a role not only in motor, but also in cognitive and social cognitive functions. The aim of this study was to investigate social cognition in patients with different CDs. MATERIALS AND METHODS: Social cognition was examined in 34 patients, 12 with spinocerebellar ataxia type 1 (SCA1), 6 with spinocerebellar ataxia type 2 (SCA2), and 16 with idiopathic late onset cerebellar ataxia (ILOCA). All patients were clinically evaluated using the Scale for the Rating and Assessment of Ataxia. In addition, 34 age, sex, and education-matched healthy control (HC) subjects were similarly analyzed. Social cognition was studied using two tests: the Faux Pas Recognition Test and the Reading the Mind in the Eyes Test (RMET). An appropriate array of neuropsychological tests was used to assess the global cognitive status as well as the frontal functions and mood. RESULTS: CD patients achieved significantly worse results on both tests of social cognition compared to the HCs. The SCA1 + 2 group achieved the poorest results on the Faux Pas Recognition Test and exhibited poor performance on all cognitive tests, but was only significantly worse compared to the ILOCA group on the Free and Cued Selective Reminding Test (FCSRT) - recognition. The patients in the SCA1 + 2 and ILOCA groups obtained similar scores on RMET. In the SCA1 + 2 group the findings significantly correlated with clinical parameters of disease severity and duration and executive functions (EFs), and with mood and executive functions in the ILOCA group. In the SCA group EFs appeared as the only significant predictor of RMET achievement. The Boston Naming Test (BTN) was a significant predictor of the CD patients' achievement on RMET, while the BTN, the Trail Making Test Part A and FCSRT - Delayed free recall predicted their performance on the Faux Pas Recognition Test. CONCLUSION: Patients with CD have social cognitive impairments as demonstrated by the Faux Pas Test and the RMET test results. The SCA1 and 2 patients exhibited a more pronounced impairment compared with the ILOCA patients. The independent cognitive predictors of social cognition impairment were EFs and language.

Childhood maltreatment correlates with higher concentration of transforming growth factor beta (TGF-ß) in adult patients with major depressive disorder.

Transforming growth factor beta (TGF-ß), which has a role as a regulatory cytokine, has not been widely investigated in patients with major depressive disorder (MDD) who experienced childhood trauma. The aim of our study was to investigate the differences in circulating TGF-ß levels between the patients with major depressive disorder (MDD) with and without child maltreatment (CM) history, and to compare them to the corresponding control subjects' groups (with or without CM). Blood samples were obtained from 55 patients, fulfilling DSM-IV-R criteria for a current MDD episode without psychotic symptoms, and 45 healthy controls, matched for age and gender. Participants were administered the Childhood Trauma Questionnaire (CTQ). Serum TGF-ß concentration was determined by enzyme-linked immunosorbent assay. The concentration of TGF-ß was significantly higher in patients with MDD with CM history, compared to MDD patients with no CM, as well as both control groups. Furthermore, we have shown that the combined effect of CM history and MDD affected TGF-ß levels in adulthood, which was not observed in the control group with CM. These results indicate that MDD patients with the experience of CM have altered immune-regulatory response, and they may constitute a specific subtype within this heterogenic disorder (ecophenotype).

Impact of depression on gait variability in Parkinson's disease.

OBJECTIVE: The goal of this study was to analyze how depression associated with Parkinson's disease (PD) affected gait variability in these patients using a dual-task paradigm. Additionally, the dependency of the executive functions and the impact of depression on gait variability were analyzed. PATIENTS AND METHODS: Three subject groups were included: patients with PD, but no depression (PD-NonDep; 14 patients), patients with both PD and depression (PD-Dep; 16 patients) and healthy controls (HC; 15 subjects). Gait was recorded using the wireless sensors. The participants walked under four conditions: single-task, motor dual- task, cognitive dual-task, and combined dual-task. Variability of stride length, stride duration, and swing time was calculated and analyzed using the statistical methods. RESULTS: Variability of stride duration and stride length were not significantly different between PD-Dep and PD-NonDep patients. The linear mixed model showed that swing time variability was statistically significantly higher in PD-Dep patients compared to controls (p = 0.001). Hamilton Disease Rating Scale scores were significantly correlated with the swing time variability (p = 0.01). Variability of all three parameters of gait was significantly higher while performing combined or cognitive task and this effect was more pronounced in PD-Dep group of patients. CONCLUSIONS: Depression in PD was associated with swing time variability, and this effect was more prominent while performing a dual-task. SIGNIFICANCE: Diagnosing and treating depression might be important for gait improvement and fall reduction in PD patients.

Determinants of quality of life among individuals seeking mental health care after termination of state of emergency due to the coronavirus disease 2019 pandemic.

ABSTRACT: Prompted by the need to measure the impact of the coronavirus disease 2019 on main areas of quality of life related to mental health (MH), the COV-19-impact on quality of life (COV19-QoL) scale has been developed recently. We measured how patients seeking face-to-face MH care perceived the coronavirus disease 2019 impact on QoL and how socio-demographic factors, stress, and personality contributed to QoL in this diagnostically diverse population.Patients aged 18 to 65 years (n = 251) who came for the first time to the outpatient units during the 6-week index-period (May 21-July 1, 2020) were included. The cross-sectional assessment involved sociodemographic variables, working diagnosis, personality traits (7-dimension model, including HEXACO and DELTA), stress (list of threatening experiences and proximity to virus), and COV19-QoL.The perceived impact of the pandemic on QoL was above the theoretical mean of a 5-point scale (COV19-Qol = 3.1 ±â€Š1.2). No association between total COV19-QoL score, sociodemographic parameters, and working diagnoses was found in the present sample. After testing whether positional (threatening experiences), or dispositional (personality) factors were predominant in the perceived impact of COV-19 on QoL, significant predictors of the outcome were personality traits Disintegration (B = 0.52; P < .01) and Emotionality (B = 0.18; P < .05).It seems that pervasiveness and uncertainty of the pandemic threat triggers-especially in those high on Disintegration trait-a chain of mental events with the decrease of QoL as a final result. Present findings could be used to establish a profile of MH help seeking population in relation to this biological disaster, and to further explore QoL and personality in different contexts.

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Higher concentration of interleukin 6 - A possible link between major depressive disorder and childhood abuse.

Little is known about the correlation between IL-6 and childhood abuse and neglect which may be risk factors for the development of affective disorders in adulthood. The aim of this study was to analyze differences in serum concentrations of IL-6 between patients with major depressive disorder and healthy controls, and to investigate possible correlations with adverse childhood experiences. Peripheral venous blood samples were obtained from 64 patients who fulfilled DSM-IV-R criteria for a current major depressive episode without psychotic symptoms (MDD) and 53 healthy controls, matched for age and gender. Participants were assessed by the Beck Depression Inventory (BDI), Childhood Trauma Questionnaire (CTQ), Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS). The concentration of IL-6 was significantly higher in patients with major depressive disorder compared to healthy controls. The total score of childhood trauma questionnaire highly statistically significantly correlated with IL-6 levels in patient group. Persons who were physically abused, physically neglected and emotionally abused had higher levels of IL-6. Interleukin 6 as a pro-inflammatory immune marker could be an important developmental mediator linking physical and emotional abuse in early life with the development of depressive disorder in adulthood.

A pilot study on predictors of brainstem raphe abnormality in patients with major depressive disorder.

BACKGROUND: Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. AIM: The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. METHODS: TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls. RESULTS: The TCS detected BR abnormalities were significantly more frequent in MDD patients (35 out of 53; 66%) in comparison to matched controls (5 out of 56; 9%). The prevalence of short allele (s) homozygocity in the length polymorphism of the promoter region of the serotonin transporter gene (5-HTTLPR) was significantly higher in MDD patients relative to those with normal BR echogenicity. A stepwise statistical discriminant analysis revealed statistically significant separation between MDD patients with and without BR abnormalities groups based on the four predictors combined: the Hamilton Anxiety Rating Scale item 5 ("difficulty in concentration, poor memory"), presence of social phobia, s allele homozygocity of the 5-HTTLPR polymorphism, and presence of generalized anxiety disorder. LIMITATIONS: Cross-sectional design and heterogenous treatment of depressed patients. CONCLUSIONS: Reduced BR echogenicity in at least a subgroup of MDD patients may reflect a particular phenotype, characterized by more prevalent comorbid anxiety disorders, associated with particular genetic polymorphisms and neurotransmitter(s) deficits, most probably altered serotonergic mechanisms.

Posttraumatic Stress Disorder after Vaginal Delivery at Primiparous Women.

Although severe gynaecological pathology during delivery and negative outcome have been shown to be related with posttraumatic stress disorder (PTSD) little is known about traumatic experiences following regular delivery, at the expected time and with a healthy child. The objective of our study was to determine the prevalence of PTSD during postpartum period after vaginal delivery and its risk factors. The sample included 126 primiparous women. Monthly, for the next three months, the women were assessed for PTSD using the gold standard interview for PTSD, Clinician-Administered PTSD Scale (CAPS). Risk factors were assessed including sociodemographic variables, personal medical history and clinical variables. After the first month, 2.4% women had acute full PTSD and another 9.5% had clinically significant level of PTSD symptoms. Following the second and the third month, partial PTSD was found in 5.9% and 1.3% of the women, respectively, and none of participants had full PTSD. Obstetrical interventions were the only significant risk factor for the development of PTSD. Symptoms of postpartum PTSD are not rare after a traumatic delivery, and associated with specific obstetrical risk factors. Awareness of these risk factors may stimulate interventions to prevent this important and neglected postpartum disorder.

Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study.

OBJECTIVE: To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. METHODS: We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews. RESULTS: Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. CONCLUSION: The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.

Sex differences in autism spectrum disorders: does sex moderate the pathway from clinical symptoms to adaptive behavior?

We explored sex differences in diagnostic categories, clinical symptoms and adaptive behavior of persons with autism spectrum disorders, as well as sex-specific correlations of clinical and adaptive caracteristics. The study involved 108 patients (83 males, 6.73 ± 4.33 years old) diagnosed with autism spectrum disorders (ASD). Assessment included ADI-R and Vineland Adaptive Behavior Scale II. Males were more often diagnosed with typical autism. There were no sex differences in the autistic symptoms, while females showed better functioning in Daily living skills, without reaching statistically significant difference (p = 0.062). We have found different associations of autistic symptoms with different aspects of adaptive behavior in males and females. Social reciprocity in females correlated with social domain of adaptive behavior, in a positive direction. Our findings have shown that although there are no sex differences in autistic symptoms, females tend to be somewhat more functional, and are also less frequently diagnosed with typical autism. Our results have also shown that sex might moderate the way clinical symptoms are expressed in adaptive behavior. Social reciprocity might be the core feature regarding sex differences in ASD. Our findings might have diagnostic and therapeutical implications, pointing out to the need for individualized, sex-specific treatment in this group of disorders.

Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity.

An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits.