Subjective Cognitive Complaints in Unaffected First-Degree Relatives of Schizophrenia Patients: Relation to Cognitive Performance, Psychotic Experiences, and Social Functioning.

Background: Neurocognitive deficits are well-documented in patients of schizophrenia and their first-degree relatives (FDRs). Metacognitive awareness of these deficits, called neurocognitive insight (NI), has been found to be poor in schizophrenia patients but has not been assessed in their FDRs. This study evaluated NI and its relationship with objective cognitive performance, a history of psychotic experiences (PEs), and social functioning in unaffected FDRs. Methods: This cross-sectional study was conducted at the outpatient department of a tertiary care teaching hospital. A total of 100 FDRs were assessed for PEs and evaluated for subjective cognitive complaints (SCC), objective cognitive performance, and social functioning using the Subjective Scale to Investigate Cognition in Schizophrenia, neurocognitive tests from the National Institute of Mental Health and Neurosciences battery, and SCARF Social Functioning Index, respectively. Results: Compared to normative data, episodic memory was the most commonly impaired domain (up to 72% of participants), followed by working memory, attention, and executive function. There was no correlation between SCC and neuropsychological test scores in the corresponding cognitive domains, implying poor NI. 15% of participants had a lifetime history of PEs. This group had significantly higher SCC as compared to those without PEs (U = 0.366, P = 0.009, r = 0.26). A regression analysis showed that the FDRs' social functioning reduced by 0.178 units for each unit increase in SCC [F (1,98) = 5.198, P = 0.025]. Conclusion: Similar to schizophrenia patients, FDRs also have poor NI. The severity and progression of SCC could be explored as a possible marker for screening and monitoring FDRs at an ultrahigh risk for psychosis. Importantly, even in unaffected FDRs, SCC could affect socio-occupational functioning and need further research.

Subjective cognitive complaints and its relation to objective cognitive performance, clinical profile, clinical insight, and social functioning in patients of schizophrenia: A cross-sectional study.

CONTEXT: Neurocognitive deficits are well documented in schizophrenia. Neurocognitive insight (NI), described as awareness of neurocognitive deficits, has not been evaluated in the Indian context. Its relation to clinical profile and social functioning also remains unexplored. AIMS: The aim of this study was to evaluate the subjective cognitive complaints (SCCs) and their relation to objective cognitive performance, clinical profile, clinical insight, and social functioning in patients of schizophrenia. SETTINGS AND DESIGN: This was a cross-sectional study at the outpatient department of a tertiary care teaching hospital. MATERIALS AND METHODS: One hundred individuals with schizophrenia were evaluated using Positive and Negative Syndrome Scale, Subjective Scale To Investigate Cognition in Schizophrenia, abbreviated version of Scale to Assess Unawareness in Mental Disorders, and Schizophrenia Research Foundation-Social Functioning Index. Cognitive performance was assessed using (1) Digit Span Test (attention) from Wechsler Adult Intelligence Scale, 3rd edition and (2) Passages Test (explicit memory), (3) Verbal n-back Test (working memory), and (4) Stroop Test (executive functioning) from the National Institute of Mental Health and Neuro Sciences Battery. STATISTICAL ANALYSIS: Statistical analysis was done using descriptive statistics, nonparametric tests, and Pearson's coefficient of correlation. RESULTS: Participants showed impairment in all cognitive domains. Except for working memory, there was no correlation between SCC and objective performance for other cognitive domains correspondingly, implying poor NI. Severity of psychosis and clinical insight did not have any correlation with SCC. Higher SCC correlated with poorer social functioning, especially in "occupational" and "other social roles" domains. CONCLUSIONS: Individuals with schizophrenia have poor NI. This is independent of severity of psychosis or clinical insight into illness. Socio-occupational functioning and depression should be actively enquired into when patients present with SCC.

Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/µl) in adult dengue - Results of a pilot study.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/µL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/µL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/µL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.

Psychopathology and personality factors in first-degree relatives of patients with schizophrenia.

BACKGROUND: Schizophrenia is a chronic mental illness which has far-reaching consequences not only on patients but also on relatives. These relatives are at an increased risk for developing schizophrenia, depression, and substance dependence. Psychopathology may be related to personality factors. This study was planned to assess psychopathology and personality factors in first degree relatives of patients with schizophrenia and to evaluate any relation between them. MATERIALS AND METHODS: This was a cross-sectional study conducted at psychiatry out- and in-patient clinic at a tertiary care teaching hospital. One hundred and fifty patients who were first-degree relatives of patients diagnosed with schizophrenia on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition were enrolled in this study. Psychopathology was assessed on "Symptom Checklist 90-Revised." "Big Five Inventory" (BFI) was used to study the personality factors. The two variables were compared to look for any relation between them. RESULTS: Eighty-two of 150 (54.67%) first-degree relatives were diagnosed to have significant psychopathology. Among them, 42 (i.e., 58.5%) had either somatization or depression. Those relatives who had psychopathology scored higher on neuroticism (P = 3.51E-04) and lower on agreeableness (P = 0.029) domains of BFI. CONCLUSION: Relatives of patients with schizophrenia should be screened for psychopathology regularly, also relation between personality and psychopathology needs to be explored further.

Psychopathology and coping mechanisms in parents of children with intellectual disability.

BACKGROUND: Raising a child with intellectual disability (ID) can add to parenting stress significantly. This stress can manifest into psychopathologies such as anxiety and depression. The aims of the study were to assess psychopathology and coping mechanisms in parents of children with ID. MATERIALS AND METHODS: A total of 100 consecutive consenting parents of children with ID were interviewed from child psychiatry outpatient department of a municipal-run tertiary care teaching hospital. A semi-structured pro forma, symptom checklist 90 revised (SCL90R) and Mechanism of Coping Scale (MOCS) were used for assessment. RESULTS: Mean age for the parents was 37.02 (±7.35) years, and for the children, it was 8.29 (±3.11) years. There were 60 mothers and 61 parents of a male child among sample. Eighty-five of parents considered their child's ID to be a major concern in their life. Depression had highest mean among psychopathologies. Mothers had higher score for depression and Interpersonal-sensitivity. Parental psychopathology did not differ significantly with severity of ID of child. Global severity index of SCL90R correlated negatively with age of parents (P = 0.015) and positively with fatalism (P = 0.004), expressive-action (P < 0.000) and passivity (P = 0.001) coping mechanisms. CONCLUSION: Depression is the most common psychopathology especially among mothers of child with ID. Psychopathology is independent of severity of ID and worsens with coping mechanisms like fatalism, expressive-action, and escape-avoidance. A child with ID should be seen and treated as a family unit giving enough attention to parent's psychological needs as well.

Study of Internet addiction in children with attention-deficit hyperactivity disorder and normal control.

BACKGROUND: In the current era, the use of electronic media in the form of Internet has increased exponentially, particularly among children, and has led to their excessive involvement in Internet. In this context, attention-deficit hyperactivity disorder (ADHD) children were found to have increased tendency for this addiction. AIMS AND OBJECTIVES: The aim is to study and compare Internet addiction between ADHD and normal children and the relation of demographic profile to Internet addiction. MATERIALS AND METHODS: This was a cross-sectional study including 100 children (50 ADHD cases and 50 normal children without any psychiatric illness as controls) between the ages of 8 and 16 years. A semi-structured pro forma for demographic profile and Internet usage using Young's Internet Addiction Test (YIAT) was used. Statistical analysis was done using SPSS 20. RESULTS: Internet addiction among ADHD children was 56% (54% having "probable Internet addiction" and 2% having "definite Internet addiction"). This was statistically significant (P < 0.05) in comparison with normal children where only 12% had Internet addiction (all 12% had "probable Internet addiction"). ADHD children were 9.3 times more prone to the development of Internet addiction as compared to normal (odds ratio - 9.3). Significant increase in average duration of Internet usage in ADHD children with increasing score of YIAT (P < 0.05) was seen. The incidence of Internet addiction was more in male ADHD children as compared to normal (P < 0.05). CONCLUSIONS: ADHD children are more prone to Internet addiction as compared to normal children and thus require preventive strategies.

Epileptic Encephalopathy and Autism: A Complex Interplay.

Drug-resistant epileptic encephalopathy such as Dravet syndrome presents with autistic symptoms. Three cases with autism spectrum disorder with comorbid Dravet syndrome were assessed. All the cases presented with onset of seizures before a year and with autistic features. The patients responded to a combination of antiepileptic drugs (AEDs), resulting in reduced frequency of seizures and behavioral issues. Contrary to the belief that both epilepsy and use of AEDs have adverse impact on the cognition of children with an early onset of epilepsy, we found improvement in the symptoms of our patients who presented with autism and epilepsy. Primary treatment approaches such as occupational therapy, special education, speech therapy, and behavioral therapy; effective diagnosis of comorbidities such as epilepsy; and aggressive treatment might help with behavioral improvement. Early diagnosis followed by treatment with AEDs can improve seizures, electroencephalography abnormalities, and behavioral problems.

Study of Spirituality in Elderly With Subjective Memory Complaints.

Subjective memory complaints are very common among elderly. They can be due to depression, cognitive decline, or be a part of normal aging process. Spirituality is another important dimension in elderly, and it is believed to help them cope with various adversities. This study was done to find out whether any relation exists between these 2 variables in elderly. A total of 120 elderly individuals, presenting with subjective memory complaints, were divided into 3 groups - controls, elderly with depression, and elderly with mild cognitive impairment (MCI). Spirituality in them was studied by dividing it into the subdomains of self-transcendence, presence of meaning in life, search for meaning in life, and locus of control. Spirituality was the highest in controls, followed by MCI group, and then depression group. Spirituality had a direct negative relationship with severity of depression, while relationship of spirituality with severity of cognitive decline was more complex. Relationship of spirituality with mental health status in elderly patients seemed bidirectional, that is, cause as well as effect relationship.

Psychiatry and law: past, present and future.

It is important that every citizen knows the law of the state. Psychiatry and law both deal with human behaviour. This paper attempts to highlight the interplay between these two by discussing about various legislations like The Family Courts Act 1984, Narcotic Drugs and Psychotropic Substances Act 1985, Juvenile Justice Act 1986, Consumer Protection Act 1986, Persons with Disability Act 1995, The Maintenance and Welfare of Senior Citizens Act 2007.

Psychosocial profile of male patients presenting with sexual dysfunction in a psychiatric outpatient department in Mumbai, India.

INTRODUCTION: Sexual dysfunction can occur due to biological problems, relationship problems, lack of proper sexual knowledge or a combination of these. India is often known as the land of Kamasutra. But as far as sexuality research is concerned, there is a paucity of relevant data from India. In view of this, we conducted a study to assess the psychosocial profile of males presenting with sexual dysfunction to psychiatry out-patient department of a tertiary medical hospital. MATERIALS AND METHODS: Hundred consecutive male patients presenting with sexual dysfunction were screened using Arizona Sexual Experiences Scale for clinical sexual dysfunction and after obtaining their informed consent were included in this study. They were assessed using a semi-structured proforma, Diagnostic and Statistical Manual of Mental Disorders, 4(th) Edition, Text Revision criteria, Mini-International Neuropsychiatric Interview, and Dyadic Adjustment Scale. RESULTS: Majority of our respondents were in the 18-30 years age group and were married. The main source of sex knowledge for 69% of them was peer group. Age of onset of masturbation was 11-13 years for 43% of them. Premature ejaculation was the most common sexual dysfunction seen in the respondents. Marital discord was seen in significantly lesser number of respondents (32.35%) as also major depressive disorder that was seen in only 16%. DISCUSSION: Premature ejaculation was the most common sexual dysfunction in our sample. Despite the sexual dysfunction, marital discord and depression were seen less commonly in our respondents.

Low serum iron as a possible risk factor for neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a rare, but fatal condition characterized by rigidity, fever, dysautonomia and altered consciousness along with elevated serum creatinine phosphokinase levels and leukocytosis. Treatment of NMS includes symptomatic and specific treatment with drugs like bromocriptine may be given. Risk factors for NMS include dehydration, parenteral antipsychotics and high potency antipsychotics. One of the important, but lesser known risk factors for NMS is low serum iron. Pronounced reduction in serum iron suggests that acute phase reactants do have a role in NMS. The present case report focuses on the importance of low serum iron as a risk factor for NMS.

Evaluation of effectiveness of integrated intervention in autistic children.

OBJECTIVES: To assess the effectiveness of integrated therapy over the past 3 y on the recipient autistic children and its correlation with the following variables - age at admission, duration of therapy given and initial severity of symptoms. METHODS: The index study was a retrospective study with 18 autistic children as subjects; the maximum duration of intervention was 3 y. The integrated approach consisted of special education using principles of applied behavior analysis, occupational and speech therapy. The progress records, the occupational therapy and the speech therapy progress reports were tabulated as data. The Childhood Autism Rating Scale (Schopler, Reichler and Renner, 1986) was used for evaluation of severity of symptoms at admission and in present day. The data was then compared and analyzed. RESULTS: The present study showed significant positive results. Only few domains requiring very high integrated cognitive and sensorimotor functioning showed non-significant results. Age at intervention correlated negatively and, duration of therapy given and initial severity of symptoms correlated positively with effectiveness of therapy. CONCLUSIONS: Continuous feedback and modification of the therapy is required to maintain performance and develop target interventions for problematic areas identified. Longitudinal as well as comparative studies are required to better understand the benefits of integrated approach.

A study on the prevalence of internet addiction and its association with psychopathology in Indian adolescents.

BACKGROUND: There has been an explosive growth of internet use not only in India but also worldwide in the last decade. There is a growing concern about whether this is excessive and, if so, whether it amounts to an addiction. AIM: To study the prevalence of internet addiction and associated existing psychopathology in adolescent age group. MATERIALS AND METHODS: A cross-sectional study sample comprising of 987 students of various faculties across the city of Mumbai was conducted after obtaining Institutional Ethics Committee approval and permission from the concerned colleges. Students were assessed with a specially constructed semi-structured proforma and The Internet Addiction Test (IAT; Young, 1998) which was self-administered by the students after giving them brief instructions. Dukes Health Profile was used to study physical and psychosocial quality of life of students. Subjects were classified into moderate users, possible addicts, and addicts for comparison. RESULTS: Of the 987 adolescents who took part in the study, 681 (68.9%) were female and 306 (31.1%) were males. The mean age of adolescents was 16.82 years. Of the total, about 74.5% were moderate (average) users. Using Young's original criteria, 0.7% were found to be addicts. Those with excessive use internet had high scores on anxiety, depression, and anxiety depression. CONCLUSIONS: In the emerging era of internet use, we must learn to differentiate excessive internet use from addiction and be vigilant about psychopathology.

Comparison of self-esteem and maternal attitude between children with learning disability and unaffected siblings.

OBJECTIVES: To compare self-esteem and maternal attitude between children with learning disability and their unaffected siblings. METHODS: This cross sectional study was conducted at a tertiary care hospital in an urban setting. It comprised of 31 pairs of children with a learning disability, their unaffected siblings and input from their mothers. All children were assessed with Rosenberg self-esteem scale. Mothers were asked to fill Index of parental attitude (IPA) and semi structured proforma with demographic data and questionnaire about her children with a learning disability and his/her unaffected sibling. RESULTS: Self-esteem was found to be lower in children with learning disability. They felt they do not have much to be proud of and have a fewer number of good qualities. They are also inclined to consider themselves as failures. In factors affecting self-esteem, index of parental attitude was found to be unfavorable towards children with learning disability. Mothers felt child was interfering with their activities and was getting on their nerves. In addition, they also felt that they do not understand their child, feel like they do not love their child and wished that child was more like others they know off. More academic failures, academic difficulties and negative school report were also perceived by mother as lowering child's self-esteem. CONCLUSIONS: Self-esteem was lower in children with learning disability. In factors affecting self-esteem maternal attitude, academic difficulties, academic failure and negative school reports was found to be unfavorable.

Study of emotional intelligence and empathy in medical postgraduates.

OBJECTIVES: The important domains of emotional intelligence (EI) are self-awareness and control of emotions, motivating oneself, and empathy. These are necessary to handle any relationship. This study aims to (i) assess emotional intelligence focusing specifically on empathy; (ii) to study the level of anger; and (iii) correlating level of anger with (a) EI and (b) empathy in medical postgraduates. MATERIALS AND METHODS: Subjects were assessed randomly after obtaining informed consent, through semi-structured proforma and various scales, including Emotional Quotient Self-Assessment Checklist, Multi-Dimensional Emotional Empathy Scale, and Clinical Anger Scale. Data was analyzed using multivariate analysis with analysis of covariance test. RESULTS: On Emotional Quotient Self-Assessment checklist, more than 70% had poor emotional intelligence. Married males in the study were more confident and empathizing. Those with some major problem at home were more aware of their own emotions and other's feelings. Residents who had voluntarily chosen their specialty postgraduation training course (eg, medicine, surgery, and others), those who had less work load, those who had time for recreational activities, and exercise had scored high on EI. Good control of emotions in self was associated with good relationship with superiors and colleagues. Score on Clinical anger was moderate to severe in 10.6% of the subjects. EI and clinical anger correlated negatively.

Tip60-mediated acetylation activates transcription independent apoptotic activity of Abl.

BACKGROUND: The proto-oncogene, c-Abl encodes a ubiquitously expressed tyrosine kinase that critically governs the cell death response induced by genotoxic agents such as ionizing radiation and cisplatin. The catalytic function of Abl, which is essential for executing DNA damage response (DDR), is normally tightly regulated but upregulated several folds upon IR exposure due to ATM-mediated phosphorylation on S465. However, the mechanism/s leading to activation of Abl's apoptotic activity is currently unknown. RESULTS: We investigated the role of acetyl modification in regulating apoptotic activity of Abl and the results showed that DNA strand break-inducing agents, ionizing radiation and bleomycin induced Abl acetylation. Using mass spectrophotometry and site-specific acetyl antibody, we identified Abl K921, located in the DNA binding domain, and conforming to one of the lysine residue in the consensus acetylation motif (KXXK--X3-5--SGS) is acetylated following DNA damage. We further observed that the S465 phosphorylated Abl is acetyl modified during DNA damage. Signifying the modification, cells expressing the non acetylatable K921R mutant displayed attenuated apoptosis compared to wild-type in response to IR or bleomycin treatment. WT-Abl induced apoptosis irrespective of new protein synthesis. Furthermore, upon γ-irradiation K921R-Abl displayed reduced chromatin binding compared to wild type. Finally, loss of Abl K921 acetylation in Tip60-knocked down cells and co-precipitation of Abl with Tip60 in DNA damaged cells identified Tip60 as an Abl acetylase. CONCLUSION: Collective data showed that DNA damage-induced K921 Abl acetylation, mediated by Tip60, stimulates transcriptional-independent apoptotic activity and chromatin-associative property thereby defining a new regulatory mechanism governing Abl's DDR function.

Gliotoxin causes apoptosis and necrosis of rat Kupffer cells in vitro and in vivo in the absence of oxidative stress: exacerbation by caspase and serine protease inhibition.

BACKGROUND/AIMS: A potential application of gliotoxin therapy for liver fibrosis was suggested by its apoptotic effect on fibrogenic activated stellate cells. We investigated if gliotoxin exerts similar effects on hepatic macrophage Kupffer cells. METHODS: Effects of gliotoxin on Kupffer cells isolated from the normal liver and in vivo following its administration to CCl(4)-induced cirrhotic rats were studied. RESULTS: Gliotoxin caused apoptosis of cultured Kupffer cells, the effect being apparent at 0.3 microM concentration within 1h; longer incubation caused necrosis. This effect was associated with mitochondrial cytochrome c release, caspase-3 activation and ATP depletion. Interestingly, inhibition of caspase-3 and serine proteases accelerated and augmented gliotoxin-induced cell death via necrosis. Gliotoxin stimulated nuclear translocation of NFkappaB, and phosphorylation of p38, ERK1/2 and JNK MAP kinases, but these signaling molecules were not involved in gliotoxin-induced death of Kupffer cells. In vivo administration of gliotoxin to cirrhotic rats caused apoptosis of Kupffer cells, stellate cells and hepatocytes. In control rats, the effect was minimal on the nonparenchymal cells and not apparent on hepatocytes. CONCLUSIONS: In the fibrotic liver, gliotoxin nonspecifically causes death of hepatic cell types. Modification of gliotoxin molecule may be necessary for selective targeting and elimination of activated stellate cells.

c-Abl kinase regulates curcumin-induced cell death through activation of c-Jun N-terminal kinase.

Curcumin, a natural phenolic compound found in turmeric (Curcuma longa) exhibits anticancer properties, attributed to its antiproliferative and apoptosis-inducing activity. The ubiquitously expressed nonreceptor tyrosine kinase c-Abl regulates stress responses induced by oxidative agents such as ionizing radiation and H2O2. In this study, we show that c-Abl is an important component of the cell death response activated by curcumin and that Abl mediates this response partly through activation of c-Jun N-terminal kinase (JNK). Therefore, inhibition of Abl by STI571 [imatinib (Gleevec)] treatment or down-regulation of Abl expression through Abl-specific short-hairpin RNA (shRNA) diminished cell death induction and JNK activation. Highlighting the interdependent nature of the Abl and JNK signaling in the curcumin-induced cell death response, a JNK inhibitor [anthra(1,9-cd)pyrazol-6(2H)-one-1,9-pyrazoloanthrone (SP600125)] caused very little cell death inhibition in STI571-pretreated cells and in Abl shRNA-expressing cells. Moreover, treatment with Abl and JNK inhibitor alone or together caused similar levels of cell death inhibition. Although p53 induction in response to curcumin treatment is dependent on Abl, we found that Abl-->p53 signaling is not necessary for curcumin-induced cell death. Taken together, the results demonstrate the differential roles played by Abl-->p53 and Abl-->JNK signaling events in modulating the cell death response to curcumin.