Vivek Benegal

Gray matter volume abnormalities and externalizing symptoms in subjects at high risk for alcohol dependence.

Reduced right amygdala volumes have been reported in young, alcohol‐naïve subjects at high risk (HR) for alcohol dependence. The differences in brain morphometry have been associated with an excess of externalizing behaviors in these subjects. This may reflect a neurobiological vulnerability to alcohol dependence. Existing Magnetic Resonance Imaging (MRI) studies on these subjects have examined only a few, pre‐selected brain regions using the manual regions of interest (ROI) approach. MRI of HR subjects (n = 20) and age, sex, and handedness‐matched low‐risk (LR) subjects (n = 21) were analyzed using optimized voxel‐based morphometry and ROI approach. The externalizing symptoms of these subjects and their fathers were measured using the Semi‐Structured Assessment for the Genetics of Alcoholism. HR subjects had significantly smaller volumes of superior frontal, cingulate and parahippocampal gyri, amygdala, thalamus and cerebellum. These gray matter volumes correlated negatively with externalizing symptoms scores. Subjects at HR for alcoholism have reduced volumes of critical areas of brain gray matter, which are associated with increased externalizing symptoms. These represent key endophenotypes of alcoholism.

Substance use and addiction research in India

Substance use patterns are notorious for their ability to change over time. Both licit and illicit substance use cause serious public health problems and evidence for the same is now available in our country. National level prevalence has been calculated for many substances of abuse, but regional variations are quite evident. Rapid assessment surveys have facilitated the understanding of changing patterns of use. Substance use among women and children are increasing causes of concern. Preliminary neurobiological research has focused on identifying individuals at high risk for alcohol dependence. Clinical research in the area has focused primarily on alcohol and substance related comorbidity. There is disappointingly little research on pharmacological and psychosocial interventions. Course and outcome studies emphasize the need for better follow-up in this group. While lack of a comprehensive policy has been repeatedly highlighted and various suggestions made to address the range of problems caused by substance use, much remains to be done on the ground to prevent and address these problems. It is anticipated that substance related research publications in the Indian Journal of Psychiatry will increase following the journal having acquired an ‘indexed’ status.

Corpus callosum abnormalities associated with greater externalizing behaviors in subjects at high risk for alcohol dependence

Subjects at high risk for alcoholism have a greater propensity for externalizing behaviors and brain volume reductions of possible neurodevelopmental origin. Morphometric deficits in the corpus callosum (CC), which might reflect this neurodevelopmental abnormality, have been reported in other externalizing disorders such as attention deficit hyperactivity disorder, but not in subjects at high risk for alcoholism. The objective of the current study was to evaluate the CC morphometry in subjects at high risk for alcoholism. Magnetic resonance images of the CC in high-risk subjects (n=20) were compared with those of low-risk subjects matched to the high-risk subjects for age, sex, and handedness (n=20). Mid-sagittal areas of the CC, genu, body, isthmus and splenium were measured based on Witelsons method with good inter- and intra-rater reliability. Externalizing behaviors were assessed using the Semi-Structured Assessment for Genetics of Alcoholism-II. Total CC, genu and isthmus areas were significantly smaller in high-risk than low-risk subjects after controlling for age and intracranial area. The total externalizing symptoms score had a significant negative correlation with genu and isthmus areas. Smaller CC areas and their negative association with externalizing behaviors may represent yet another marker of susceptibility to alcoholism in high-risk subjects.

Alcohol Use and Implications for Public Health: Patterns of Use in Four Communities

Background: Alcohol is one of the leading causes of death and disability globally and in India. Information on quantum and pattern of consumption is crucial to formulate intervention programs. Objectives: To identify the extent and pattern of alcohol use in urban, rural, town and slum populations using a uniform methodology. Materials and Methods: Door-to-door survey was undertaken and simple random sampling methodology was adopted; households were the primary sampling unit. One respondent in each alcohol-user household was randomly chosen for detailed interview. Results: Overall, 13% of males and females consumed alcohol. Proportion of users was greater in town (15.7%) and among 26–45 years (67.4%). Whisky (49%) and arrack (35%) were the preferred types and the preferences differed between rural (arrack) and urban (beer) areas. Nearly half (45%) of rural population were very frequent users (consuming daily or every alternate-days) as against users in town (23%) or slum (20%). Two-thirds were long-term users and the proportions were greater in the rural and town areas. While, overall 17% of the users were heavy-users, frequent-heavy-drinking was more in slum and rural areas. Nearly two-thirds consumed alcohol in liquor-shops, restaurants, bars and pubs. Habituation and peer-pressure were the key reasons for alcohol use. Conclusions: The study documented alcohol use and patterns of use in four different communities particularly in transitional areas using similar methodology. Many of the patterns identified are detrimental to health both immediate and over the long period of time.

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.

Association analysis of CAG repeats at the KCNN3 locus in Indian patients with bipolar disorder and schizophrenia.

Bipolar affective disorder and schizophrenia are severe behavioral disorders with a lifetime risk of approximately 1% in the population worldwide. There is evidence that these diseases may manifest the phenomenon of anticipation similar to that seen in diseases caused by trinucleotide repeat expansions. A recent report has implicated a potassium channel-coding gene, KCNN3, which contains a polymorphic CAG repeat in its coding region, in schizophrenia and bipolar disorder. We have tried to confirm these findings in Indian patients suffering from bipolar disorder and schizophrenia. No statistically significant evidence for the presence of an excess of longer alleles in the patient population, as compared to ethnically matched controls, was found. However, an analysis of the difference of allele sizes revealed a significantly greater number of patients with schizophrenia having differences of allele sizes > or = 5 when compared to normal controls. This finding may be of functional significance as the KCNN3 protein is thought to act as a tetramer, and a large difference in allele sizes would result in an asymmetric molecule with a different number of glutamine residues in each monomer. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:744-748, 2000.

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.

Serotonergic candidate genes and puerperal psychosis: an association study.

Background Altered serotonergic function is implicated in the aetiology and pathogenesis of a host of psychiatric disorders, and structural variations/polymorphisms in genes encoding the serotonin transporter and various serotonin receptor subtypes are attractive candidates to investigate the biological component underlying these disorders. Specific phenotypic subtypes, that perhaps represent homogeneous forms of the disorder, may increase the power to detect genes in complex diseases. Objective We investigated regulatory and functional polymorphic DNA markers of serotonergic candidate genes using a case–control approach in puerperal psychosis and bipolar affective disorder probands. Methods We genotyped 320 female participants (104 puerperal psychosis probands, 102 bipolar disorder participants and 114 controls) at the serotonin transporter SERT (5-HTT) 5-HTTVNTR and 5-HTTLPR locus; serotonin receptor 2A (5-HT2A)-T102C and His452Tyr loci, the serotonin receptor 2C (5-HT2C)-Cys23Ser locus, and seven unrelated Alu polymorphic markers. Results We observed an association of the puerperal psychosis phenotype with the allele 10 of 5-HTTVNTR of SERT (P=0.004) and a modest association with the genotypic frequencies of the 5-HTTLPR (P=0.036). A nominal P value of 0.006 was observed with the S-10 haplotype in the PP group as compared with bipolar affective disorder probands. Significant association was observed with bipolar affective disorder phenotype with Tyr allele of the 5-HT2A His452Tyr gene polymorphism (P=0.00043) even after a conservative multiple test correction. No association was observed, however, with the 5-HT2A T102C locus, and the distribution of the other seven Alu markers did not differ between the groups. Conclusion The association between polymorphisms in serotonergic genes (SERT and 5-HT2A, 5-HT2C) suggests that these genetic factors can modulate vulnerability to puerperal psychosis in female bipolar participants.

Idiopathic Catatonia: Validity of the Concept

Although catatonic features can be seen in various psychiatric and organic disorders, some patients with catatonia cannot be fitted into existing classification systems. In the current study various sociodemographic and clinical variables were compared between patients who presented with catatonia only (idiopathic catatonia), or with catatonia as a symptom of an identifiable underlying functional disorder. Patients seen over one year (1988) were classified into idiopathic catatonia (n = 30) and according to diagnosis (n = 35; schizophrenia n = 19, depression n = 16). There was an excess of females in the idiopathic group and the illness was of a shorter duration. There were no other differences between the groups. All subjects showed good response to ECTs and required almost the same mean number of ECTs. No clusters were observed using the average method. The current study suggests that catatonic symptoms can occur in the absence of any other identifiable psychiatric syndrome, although they cannot be otherwise differentiated from other psychiatric syndromes in which catatonia can present.

Evidence of linkage and association on 18p11.2 for psychosis

The genetic basis of bipolar disorder (BPD) and schizophrenia (SCZ) has been established through numerous clinical and molecular studies. Although often considered separate nosological entities, evidence now suggests that the two syndromes may share some genetic liability. Recent studies have used a composite phenotype (psychosis) that includes BPD, SCZ, psychosis not otherwise specified, and schizoaffective disorder, to identify shared susceptibility loci. Several chromosomal regions are reported to be shared between these syndromes (18p, 6q, 10p, 13q, 22q). As a part of our endeavor to scan these regions, we report a positive linkage and association finding at 18p11.2 for psychosis. Two‐point linkage analysis performed on a series of 52 multiplex pedigrees with 23 polymorphic markers yielded a LOD score of 2.02 at D18S37. An independent set of 159 parent offspring trios was used to confirm this suggestive finding. The TDT analysis yielded support for association between the marker D18S453 and the disease allele (χ2 = 4.829, P < 0.028). This region has been implicated by several studies on BPD [Sjoholt et al. (2004); Mol Psychiatry 9(6):621–629; Washizuka et al. (2004); Biol Psychiatry 56(7):483–489; Pickard et al. (2005); Psychiatr Genet 15(1):37–44], SCZ [Kikuchi et al. (2003); J Med Dent Sci 50(3):225–229; Babovic‐Vuksanovic et al. (2004); Am J Med Genet 124(3):318–322] and also as a shared region between the two diseases [Ishiguro et al. (2001); J Neural Transm 108(7):849–854; Reyes et al. (2002); Mol Psychiatry 7(4):337–339; Craddock et al. (2005); J Med Genet 42(3):193–204]. Our findings provide an independent validation of the above reports, and suggest the presence of susceptibility loci for psychoses in this region.