Satish Chandra Girimaji

Mutations in STIL, Encoding a Pericentriolar and Centrosomal Protein, Cause Primary Microcephaly

Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterized by smaller-than-normal brain size and mental retardation. MCPH is genetically heterogeneous with six known loci: MCPH1-MCPH6. We report mapping of a novel locus, MCPH7, to chromosome 1p32.3-p33 between markers D1S2797 and D1S417, corresponding to a physical distance of 8.39 Mb. Heterogeneity analysis of 24 families previously excluded from linkage to the six known MCPH loci suggested linkage of five families (20.83%) to the MCPH7 locus. In addition, four families were excluded from linkage to the MCPH7 locus as well as all of the six previously known loci, whereas the remaining 15 families could not be conclusively excluded or included. The combined maximum two-point LOD score for the linked families was 5.96 at marker D1S386 at theta = 0.0. The combined multipoint LOD score was 6.97 between markers D1S2797 and D1S417. Previously, mutations in four genes, MCPH1, CDK5RAP2, ASPM, and CENPJ, that code for centrosomal proteins have been shown to cause this disorder. Three different homozygous mutations in STIL, which codes for a pericentriolar and centrosomal protein, were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the STIL protein. Further, another recently ascertained family was homozygous for the same mutation as one of the original families. There was no evidence for a common haplotype. These results suggest that the centrosome and its associated structures are important in the control of neurogenesis in the developing human brain.

Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations.

Patients with primary microcephaly, an autosomal recessive trait, have mild to severe mental retardation without any other neurological deficits. It is a genetically heterogeneous disorder with six known loci: MCPH1 to MCPH6. Only the genes for MCPH1 and MCPH5 have been identified so far. We have ascertained nine consanguineous families with primary microcephaly from India. To establish linkage of these nine families to known MCPH loci, microsatellite markers were selected from the candidate regions of each of the six known MCPH loci and used to genotype the families. The results were suggestive of linkage of three families to the MCPH5 locus and one family to the MCPH2 locus. The remaining five families were not linked to any of the known loci. DNA‐sequence analysis identified one known (Arg117X) and two novel (Trp1326X and Gln3060X) mutations in the three MCPH5‐linked families in a homozygous state. Three novel normal population variants (i.e., c.7605G > A, c.4449G > A, and c.5961 A > G) were also detected in the ASPM gene.

Risperidone-Induced Priapism in a 12-Year-Old Boy with Schizophrenia

OBJECTIVE To examine whether adverse perinatal experiences of children are associated with obsessive compulsive disorder (OCD) in youth. METHODS Subjects were 130 children and adolescents with OCD recruited from a family genetic study of pediatric OCD and 49 matched controls from a contemporaneous family case-control study of attention-deficit/hyperactivity disorder (ADHD). Subjects were comprehensively assessed in multiple domains of function. A systematic history of pregnancy, delivery, and infancy complications was obtained. RESULTS Compared to normal controls, children with OCD had mothers with significantly higher rates of illness during pregnancy requiring medical care (chi(2) +/- 8.61, p +/- 0.003) and more birth difficulties (induced labor, forceps delivery, nuchal cord, or prolonged labor) (chi(2) +/- 7.51, p +/- 0.006). Among the OCD-affected children, we found several significant associations between adverse perinatal experiences and earlier age at onset, increased OCD severity, and increased risk for comorbid ADHD, chronic tic disorder, anxiety disorder, and major depressive disorder. CONCLUSION Although exploratory, our analyses found that children with OCD had higher rates of several adverse perinatal experiences compared with controls. Among OCD-affected children, comorbid psychopathology was predicted by specific perinatal risk factors. Prospective studies of perinatal adverse events that minimize potential recall bias and type I errors are needed.

Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations.

Bhat V, Girimaji SC, Mohan G, Arvinda HR, Singhmar P, Duvvari MR, Kumar A. Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations.

Tsunami: psychosocial aspects of Andaman and Nicobar Islands. Assessments and intervention in the early phase

The aim of this paper is to describe the activities and observations of the team from National Institute of Mental Health and Neuro Sciences (NIMHANS) Bangalore, India in the Andaman and Nicobar Islands during the early phase of the Tsunami disaster in January and February 2005. The activities comprised mental health consultation at camps, community sensitization, mental health services to the students and children, teachers orientation sessions and training of non-governmental organization [NGO] functionaries. Initial assessment reveals 5–8% of the population were suffering from significant mental health problems following the early phase of the disaster. This may increase in the aftermath of the early relief phase. Psychiatric morbidity is expected be around 25–30% in the disillusionment phase. High resilience was seen in the joint family system of tribal Nicobarese during early phase of disaster. In developing countries like India, limited availability of mental health professionals and poor knowledge about disaster mental health among the medical and para-medical staff, may lead to poor psychosocial rehabilitation of the survivors. To respond to a high magnitude natural disaster like a tsunami, the disaster mental health team must be able to understand the local culture, traditions, language, belief systems and local livelihood patterns. They also need to integrate with the network of various governmental and non-governmental organizations to cater to the needs of the survivors. Hence the presence of a disaster mental health team is definitely required during the early phase of the disaster in developing countries.

A follow-up study of juvenile obsessive-compulsive disorder from India.

Objective:  To study the long‐term course and outcome of juvenile obsessive–compulsive disorder (OCD).

Comorbidity in juvenile obsessive-compulsive disorder : A report from India

Objective: Using minimal exclusion criteria, to assess systematically the psychiatric comorbidity in children and adolescents with obsessive–compulsive disorder (OCD) and compare the findings with those of previous studies. Method: Fifty-four children and adolescents who satisfied DSM-III-R criteria for OCD were assessed using a structured interview schedule, the Childrens version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and the questionnaire for tic disorders. All 54 subjects were recruited from the Child and Adolescent Psychiatry (CAP) services of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, South India. Diagnoses were determined consensually after a review of all the available data. Results: Comorbidity was found in 69% of the sample: 22% were diagnosed with disruptive disorders; 20% met criteria for mood disorders; 19% had anxiety disorders; and 17% had tic disorders. Only 1 subject had bipolar disorder, and none had psychosis. The rates for individual diagnoses—in particular, the rates for disruptive disorders, bipolar disorder, and psychosis—were considerably lower than those reported in previous studies. Conclusions: Patterns of comorbidity in this study differed from those previously reported. Novel patterns of comorbidity with disruptive disorders, bipolar disorder, and psychosis reported in a few recent studies were not replicated in this study. These differences are probably due to different ascertainment methods. Comorbidity needs to be assessed in large epidemiological samples before definite associations can be made between certain comorbid disorders and juvenile OCD.

Comparative Study of Psychiatric Morbidity among the Displaced and Non-Displaced Populations in the Andaman and Nicobar Islands following the Tsunami

OBJECTIVE The objective of this study was to compare the psychiatric morbidity between the displaced and non-displaced populations of the Andaman and Nicobar Islands during the first three months following the 2004 earthquake and tsunami. METHODS The study was conducted at the 74 relief camps in the Andaman and Nicobar Islands. Port Blair had 12 camps, which provided shelter to 4,684 displaced survivors. There were 62 camps on Car-Nicobar Island, which provided shelter to approximately 8,100 survivors who continued to stay in their habitat (non-displaced population). The study sample included all of the survivors who sought mental health assistance inside the camp. A psychiatrist diagnosed the patients using the ICD-10 criteria. RESULTS Psychiatric morbidity was 5.2% in the displaced population and 2.8% in the non-displaced population. The overall psychiatric morbidity was 3.7%. The displaced survivors had significantly higher psychiatric morbidity than did the non-displaced population. The disorders included panic disorder, anxiety disorders not otherwise specified, and somatic complaints. The existence of an adjustment disorder was significantly higher in the non-displaced survivors. Depression and post-traumatic stress disorder (PTSD) were distributed equally in both groups. CONCLUSIONS Psychiatric morbidity was found to be highest in the displaced population. However, the incidence of depression and PTSD were distributed equally in both groups. Involvement of community leaders and survivors in shared decision-making processes and culturally acceptable interventions improved the community participation. Cohesive community, family systems, social support, altruistic behavior of the community leaders, and religious faith and spirituality were factors that helped survivors cope during the early phase of the disaster.

The Index Manic Episode in Juvenile-Onset Bipolar Disorder: The Pattern of Recovery

Objective: Recent studies of patients with juvenile bipolar disorder report low rates of recovery and high rates of chronicity. However, we lack data on the short-term outcome. This study examines the pattern of recovery from the index episode in an aggressively treated juvenile sample. Method: We assessed 25 subjects (< 16 years) with a diagnosis of mania, using the Diagnostic Interview for Children and Adolescents-Revised) (DICA-R), Young Mania Rating Scale (YMRS), and Childrens Global Assessment Scale (CGAS) at intake and at 3 and 6 months. We studied the time taken to recover from the index episode, the level of functioning, and the factors predicting them. Results: After 6 months, 24 (96%) subjects had recovered from the index manic episode. The median time to recovery was 27 days. Total episode length was significantly longer among those with previous affective episodes. Conclusions: The findings suggest that juvenile-onset mania has high rates of recovery and low rates of chronicity. These differences from the existing literature need further exploration.

Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian patients with tuberous sclerosis complex

Objective –  To find the mutation and polymorphism spectrum of TSC1 and TSC2 genes in patients affected with tuberous sclerosis complex from the Indian population.