Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses.

OBJECTIVE: Adverse childhood experiences are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of adverse childhood experiences and their relation to the age of onset of major psychiatric conditions in individuals from families that had ⩾2 first-degree relatives with major psychiatric conditions (multiplex families), identified as part of an ongoing longitudinal study. METHODS: Our sample consisted of 509 individuals from 215 families. Of these, 268 were affected, i.e., diagnosed with bipolar disorder (n = 61), obsessive-compulsive disorder (n = 58), schizophrenia (n = 52), substance dependence (n = 59) or co-occurring diagnoses (n = 38), while 241 were at-risk first-degree relatives who were either unaffected (n = 210) or had other depressive or anxiety disorders (n = 31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire and total adverse childhood experiences exposure and severity scores were calculated. RESULTS: It was seen that affected males, as a group, had the greatest adverse childhood experiences exposure and severity scores in our sample. A Cox mixed effects model fit by gender revealed that a higher total adverse childhood experiences severity score was associated with significantly increased risk for an earlier age of onset of psychiatric diagnoses in males. A similar model that evaluated the interaction of diagnosis revealed an earlier age of onset in obsessive-compulsive disorder and substance dependence, but not in schizophrenia and bipolar disorder. CONCLUSION: Our study indicates that adverse childhood experiences were associated with an earlier onset of major psychiatric conditions in men and individuals diagnosed with obsessive-compulsive disorder and substance dependence. Ongoing longitudinal assessments in first-degree relatives from these families are expected to identify mechanisms underlying this relationship.

Evaluation of resting state gamma power as a response marker in schizophrenia.

AIMS: An abnormal activity in the electroencephalography (EEG) gamma band (>30 Hz) has been demonstrated in schizophrenia and this has been suggested to be reflecting a deficit in the development and maturation of the basic cognitive functions of attention, working memory and sensory processing. Hypothesizing gamma oscillatory activity as a potential EEG biomarker to antipsychotic response in schizophrenia, the present study aimed at measuring baseline spontaneous gamma activity in schizophrenia patients, and evaluating its response to antipsychotic treatment over 8 weeks. METHODS: Fifteen drug-free/naïve patients were recruited, compared at baseline with 15 age-, sex- and education-matched healthy controls, and were followed up for 8 weeks' treatment on antipsychotics. Resting state EEG waves were recorded using high (192-channel) resolution EEG at admission, 4 weeks and 8 weeks. Spectral power was calculated using fast Fourier transformation, Hanning window. The power was averaged region-wise over nine regions in three frequency ranges (30-50 Hz, 50-70 Hz, 70-100 Hz). RESULTS: Patients and controls differed significantly at intake in terms of left temporal and parietal high (70-100 Hz) gamma power. Consequently, no significant differences were seen over the course of antipsychotic treatment on gamma spectral power in any of the regions. CONCLUSIONS: Lack of significant effect of treatment on gamma power suggests that these gamma oscillations may be trait markers in schizophrenia.

Antidepressant effects of ketamine and ECT: A pilot comparison.

BACKGROUND: To compare the antidepressant effects and cognitive adverse effects of intravenous ketamine infusion and Electro-convulsive therapy (ECT) in persons with severe depressive episodes. METHODS: This assessor-blinded randomized control trial included 25 patients (either sex; 18-65 years) meeting ICD-10 criteria for severe depression (bipolar or unipolar). Patients received either ECT (n = 13) or intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min; n = 12) for six alternate day sessions over a period of two weeks. Severity of depression was assessed at baseline and on every alternate day of intervention using the Hamilton Depression Rating Scale (HDRS) and self-reported Beck Depression Inventory (BDI). RESULTS: Baseline socio-demographic and clinical variables including HDRS (ECT: 25.15±6.58; Ketamine: 23.33±4.05, p = 0.418) and BDI (ECT: 37.07±6.58; Ketamine: 33.33±9.29; p = 0.254) were comparable. Repeated-measures analysis of variance revealed that ECT patients showed significantly greater reduction in HDRS (group*time interaction effect; F = 4.79; p<0.001) and BDI scores (group*time interaction effect; F = 3.83; p<0.01). ECT patients had higher response rate than ketamine patients [HDRS: ECT- 13/13(100%) vs ketamine- 8/12 (66.70%); p = 0.04]. This was true for remission as well [ECT- 12/13(92.30%) vs ketamine- 6/12(50%), p = 0.030; both HDRS and BDI]. Performance on Digit Symbol Substitution Test (as part of the Battery for ECT-Related Cognitive Deficits scale) significantly improved in ketamine patients (p = 0.02) while that in ECT patients worsened non significantly (p = 0.30). LIMITATIONS: Relatively small sample size; higher proportion of dropouts in the Ketamine arm. CONCLUSION: This study favoured ECT over ketamine for a better efficacy over six treatment sessions in severe depression. The results need to be replicated in larger studies. TRIAL REGISTRATION: CTRI/2019/09/021184.

Statistical power estimation in non-invasive brain stimulation studies and its clinical implications: An exploratory study of the meta-analyses.

BACKGROUND: Non-invasive brain stimulation (NIBS) techniques have emerged as a promising tool for understanding and treating psychiatric disorders, necessitating a caution in terms of interpreting research results. OBJECTIVE: This study aimed at systematically evaluating a representative sample of research conducted using NIBS interventions in neuro-psychiatric conditions, and assessing the power these studies achieved, given their sample sizes. METHODS: A database search was conducted with defined keyword combinations. Using reported summary effects of the meta-analyses as estimate of the true effects, we calculated achieved power of each individual study to detect the effect indicated by the corresponding meta-analysis. RESULTS: Findings suggest that mean and median powers in the field of NIBS were 0.50, with a mode at 0.83 (range 0.05-1.00). When analysed separately, the median powers were 0.27 for tDCS, 0.70 for TMS and 0.97 for ECT. These studies had a mean total sample size of 22.2 ±â€¯24.9 subjects and the median reported effect size across all studies was 0.61. CONCLUSION: According to our findings, studies conducted in NIBS miss around 50% of true positive results. Further, it appears that most of the researchers in this field chase statistical significance with small sample sizes, thus compromising the quality of their conclusions.

Gulliver's world: Persistent lilliputian hallucinations as manifestation of Charles Bonnet syndrome in a case of cataract and normal pressure hydrocephalus.

Charles Bonnet Syndrome (CBS) typically occurs in elderly people with peripheral vision impairment, or interruptions in the connections from eyes to visual cortex. The heterogeneity of presentations and causal mechanisms warrants clinical caution. In this report, we describe a case of CBS developing in the form of Lilliputian Hallucinations in an elderly gentleman, on the background of cataract and normal pressure hydrocephalus, the complexities arising out of such aetiogenesis, and its management. We emphasize upon the fact that CBS might develop through two concurrent mechanisms in a given individual. Treating one of these would mean persistent symptoms, and failing to recognize these would lead to continued morbidity.

Serum uric acid levels in first episode mania, effect on clinical presentation and treatment response: Data from a case control study.

Bipolar disorder (BD) patients have increased serum Uric Acid (UA) levels as compared to their healthy counterparts. They also demonstrate higher impulsivity - while symptomatic, as well as when in remission. Impulsivity adds a risk of self-harming behavior to BD, and studies show that it increases with UA levels. Given this complex relationship, the current project aimed at comparing UA levels in first-episode mania patients with matched controls, and analyzes its relationship with impulsivity, symptom severity and disease prognosis. Thirty-one first-episode mania patients were assessed on BIS-11 and YMRS, serum uric acid levels were measured, and compared to matched controls. A follow up YMRS was rated after one month to evaluate the effects of treatment. We found significantly higher levels of UA in patients, which showed positive correlation with impulsivity and a negative correlation with symptom improvement at 1 month. The results of the study support a purinergic system dysfunction hypothesis in first-episode mania, and suggest its influence on impulsivity in this patient group. Further, the mentioned dysfunction appears to have a negative impact on treatment outcomes in such cases.

Mania in Wolfram's Disease: From Bedside to Bench.

Wolfram syndrome is a relatively unexplored entity in clinical psychiatry. Historically, the discovery of a specific WFS1 gene had generated huge fanfare regarding specific genetic causations of psychiatric disorders. While the initial enthusiasm has faded now, association of Wolfram syndrome with psychiatric illnesses like schizophrenia, psychosis and suicidal behavior still remain important for understanding biological underpinnings of such disorders. We report a case of Wolfram syndrome presenting with multiple manic episodes, discuss possible genetic underpinnings for the affective symptoms and then discuss certain issues regarding management.

Electroencephalogram alpha-to-theta ratio over left fronto-temporal region correlates with negative symptoms in schizophrenia.

BACKGROUND: Negative symptoms impair outcomes on occupational functioning, social interaction and interpersonal relationships in patients with schizophrenia. Past researchers have reported reduced alpha and increased theta and delta spectral powers on quantitative EEG recordings in those with prominent negative symptoms. AIM: Present analysis aimed at exploring the relationships between lower-frequency EEG powers and negative symptoms, in schizophrenia, over a period of naturalistic antipsychotic treatment. METHOD: Fifteen right-handed drug-free/drug-naïve schizophrenia patients (N=15;M=12,F=3) were recruited and assessed on PANSS. Spontaneous 192-channel resting-state EEG was recorded at baseline, and PANSS rating was repeated at 4 weeks. Baseline EEGs of patients were compared to 15 age-sex-handedness matched controls. RESULTS: Non-significant differences emerged between patient and controls in terms of socio-demographic characteristics. Over left frontal and left temporal regions, baseline ratio of alpha/theta power (bATR) was significantly lower (p<0.001) in patients, correlated negatively with baseline PANSS negative score (PNS) (p<0.05); and over 4-weeks of antipsychotic treatment, left temporal bATR correlated positively with relative improvements in PNS. CONCLUSION: Reduced alpha power over frontal regions might imply altered arousal and/or impaired attentional process, while abnormal theta range oscillations may relate to impairments in working memory via their influences on theta-gamma coupling. Our findings suggest left-predominant deficiencies in these processes might mediate negative symptoms. Further, since ATR might reflect integrity of certain cognitive processes, those with a higher bATR might possess better cognitive resource at baseline and therefore experience greater improvement in negative symptoms with antipsychotic treatments, at least during the first 4 weeks.