Motor cortical plasticity in adolescents with early onset schizophrenia: A TMS-EMG study assessing the perturbation effect of intermittent and continuous theta burst stimulation.

BACKGROUND: Neuroplasticity in adolescents is distinct from that of adults. Literature pertaining to neuroplasticity in schizophrenia is limited to adult populations. AIM: We aimed to assess baseline (or resting) cortical excitability and cortical plasticity in adolescents with schizophrenia using the transcranial magnetic stimulation-electromyography (TMS-EMG) protocol. METHODS: Twenty adolescent cases with schizophrenia and 20 age and gender matched healthy controls were studied using a crossover design. Single pulse TMS elicited resting motor threshold (RMT) and motor evoked potentials (MEPs) were assessed. Cortical plasticity was determined by tracking MEPs after a single session continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) up to 120 min at 12 intervals. RESULTS: Baseline (or resting) cortical excitability was found to be significantly lower in cases compared with controls. Response patterns to cTBS and iTBS were similar between the crossover. While cTBS led to inhibitory response, iTBS had an excitatory effect in both the groups. In the cases, while cTBS led to significantly greater initial inhibitory response, iTBS led to significantly lower excitatory response, compared with controls. The time taken to return to baseline excitability was significantly longer after receiving cTBS for cases, compared with controls. CONCLUSIONS: iTBS and cTBS lead to excitatory and inhibitory response, representing classical long-term depression and long-term potentiation effects, respectively, in both cases and controls. We conclude that adolescents with schizophrenia have significantly lower baseline (resting) cortical excitability as well as significantly greater inhibitory plasticity; excitatory plasticity is significantly lower.

Memory changes following adjuvant temporo-parietal repetitive transcranial magnetic stimulation in schizophrenia.

OBJECTIVE: The use of repetitive transcranial magnetic stimulation (rTMS) in schizophrenia has shown improvement as well as deficits in memory. Though most studies had focused on dorsolateral prefrontal cortex only, but impact of rTMS on cognitive functions remain inconclusive. The need of the study is to assess the impact of rTMS on memory in schizophrenia. MATERIALS AND METHODS: Forty right-handed male patients with schizophrenia were included by purposive sampling and rated on Positive and Negative Syndrome Scale (PANSS) before starting the rTMS treatment with the experimental group. Low frequency 1 Hz rTMS including 1200 stimulations were given over temporo-parietal cortex for 20 min as add on to medications. At the end of 10 session treatment (5 days a week for 2 weeks), the patients were re-evaluated. RESULTS: A total of 39 patients (20 for experimental group and 19 for control group) with mean age of 29.70 ± 9.05 and 31.26 ± 7.78 years, respectively, shows significant difference to pre- and post-treatment mean PANSS score in positive, negative and general psychopathology domains. The pre- and post-treatment mean Postgraduate Institute Memory Scale Scores with multivariate repeated measures analysis of variance revealed significant improvements in all memory domains (P < 0.01) except remote memory in both experimental and control groups. CONCLUSION: RTMS in combination with antipsychotics has shown improvement in psychopathology in patients of schizophrenia without any deterioration of memory.

Quality of life after coronary artery bypass graft & percutaneous transluminal coronary angioplasty: A follow up study from India.

Coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) are treatments of choice for coronary artery disease. Quality of life (QoL) is an important factor in determining optimum treatment. This study was aimed to compare changes in QoL, six months post procedure, between CABG and PTCA, and to understand the confounding effect of various contributing factors. Thirty stable angina patients each in CABG and PTCA groups, were followed up for six months. QoL was assessed with WHO-QoL-BREF. Depression was rated on the Hamilton Depression Rating Scale. Changes in QoL and depression within and between CABG and PTCA groups were compared. Multinomial logistic regression was used to measure the predictive strength of treatment type (CABG and PTCA) on QoL, controlling for significant confounders. Although scores of QoL and depression significantly changed over time in both the groups, time×group interaction did not reach to a significance. Significant confounding effects of diabetes (P<0.01), hypertension (P<0.05) and diet restriction (P<0.05) were found. Controlling for confounding effects of these factors, group distribution to PTCA, compared to CABG, significantly predicted greater improvements in QoL (P<0.01).

Efficacy of ketamine therapy in the treatment of depression.

BACKGROUND: Severe depressive disorder is among most debilitating condition. Conventional pharmacotherapy usually takes several weeks (usually 4-12 weeks) to improve symptoms. Ketamine is an N-methyl-D aspartate receptor antagonist having rapid action on depressive symptoms. OBJECTIVES: The effect of subanesthetic dose of ketamine was assessed on depressive and anxiety symptoms. Illness severity and improvement were assessed after treatment with ketamine. MATERIALS AND METHODS: Twenty-five drug-free/naïve patients of the male sex, with severe depression having no previous history of psychotic disorder, head injury, organic disorder, cardiological problem, or substance abuse were admitted for the study. Assessments were made at baseline and injection ketamine hydrochloride was given at a subanesthetic dose of 0.5 mg/kg intravenous bolus after preparation. Assessments were repeated 1 h after the first dose. Six doses were given over 2 weeks and assessments were repeated. Final assessments were made after 1 month of the last dose. RESULTS: There was a significant improvement in depression, anxiety, and the severity of illness after 2 weeks and 1 month of the last dose of ketamine. Significant improvement at 1 st h of the first dose was seen in depression and anxiety and not for illness severity. There were transient adverse effects observed in some patients which subsided within 1 h. CONCLUSION: Ketamine has a robust and rapid effect on depression, which was seen immediately after the administration of ketamine and sustained at the end of 1 month.

Effect of adjunctive intermittent theta-burst repetitive transcranial magnetic stimulation as a prophylactic treatment in migraine patients: A double-blind sham-controlled study.

BACKGROUND: The left dorsolateral prefrontal cortex (DLPFC) seems to exert a bilateral control of chronic pain states such as migraine. Repetitive transcranial magnetic stimulation (rTMS) is known to modulate brain excitability, neurotransmitters, and endogenous opioids involved in pathophysiology of migraine. AIM: This study was designed to assess the efficacy of adjunctive intermittent theta-burst stimulation (iTBS) to the left DLPFC, as a prophylactic treatment in migraine. MATERIALS AND METHODS: The study was a double-blind, sham-controlled experiment. Patients with migraine were allotted to active (n = 20) or sham (n = 21) rTMS, respectively. Each patient received ten sessions of iTBS over the left DLPFC. Patients were rated at baseline and at 2, 4, 6, and 12 weeks after receiving the treatment. Scores were obtained from the headache diary and by applying the Migraine Disability Assessment Scale (MIDAS). RESULTS: There was a significant decrease in frequency, duration, and severity of migraine in the active group than the sham group over the study period. The effect was more pronounced during the initial 2 weeks. The MIDAS score reduced significantly in the active group than the sham group at 12 weeks. There were no significant adverse effects observed during the entire period of study. CONCLUSION: Compared to sham stimulation, adjunctive active iTBS over the left DLPFC was safe and effective in reducing the frequency, duration, and severity of migraine headache and in reducing disability associated with the illness.

Effect size of lithium, carbamazepine, and sodium valproate in child and adolescent bipolar 1 disorder during manic phase: A prospective open-label study.

AIM: The aim was to evaluate the "effect size (ES)," tolerability, and acceptability of lithium, carbamazepine, and sodium valproate in the acute phase treatment of pediatric Bipolar 1 disorder patients during manic phase. MATERIALS AND METHODS: This hospital-based, prospective, open-label study included 67 patients in manic phase of bipolar I disorder, aged 6-17 years, after informed consent by the caregivers. The patients were randomly assigned to the lithium group (n = 30), carbamazepine group (n = 20), and sodium valproate group (n = 17). They were assessed with the Schedule for Affective Disorders for School Age Children's-Present and Life time version administered to the parent and child separately, Conner's Abbreviated Rating Scale, and Cassidy Scale for Manic States (CSMS). Lithium was started in the dose of 30 mg per kg of body weight, carbamazepine in the dose of 10-20 mg/kg/day, and sodium valproate in the dose of 10-20 mg/kg body weight. Antipsychotic (chlorpromazine [CPZ] 100-500 mg per day or haloperidol up to 750 mg of CPZ equivalent) was allowed in the study. Injection haloperidol 10 mg and injection promethazine 50 mg intramuscular were allowed for initial 3-5 days to combat acute agitation. Rescue medication such as injection lorazepam 2-4 mg intramuscular was allowed throughout the study duration. The patients were rated weekly on CSMS, Bipolar Clinical Global Impression, Udvalg for kliniske Undersogelser Side Effect Rating Scale, and side effect checklist for lithium, sodium valproate, and carbamazepine, respectively. The serum level of concerned drug was obtained at weekly intervals and dose hiked, if needed to get target serum level. RESULTS: The response rate was 90% in lithium group, 70% in carbamazepine group, and 88% in sodium valproate group on the basis of ≥33% reduction from baseline CSMS. The effects of change of CSMS over the 6 weeks across the three treatment group were found to be highly statistically significant. CONCLUSIONS: In the acute phase treatment of pediatric bipolar 1 disorder patients during manic phase, the ES for lithium was 0.85, for carbamazepine 0.71, and for sodium valproate 0.84. These agents are well tolerated in treating bipolar disorder in children.

Psychiatric Comorbidity in Children with Epilepsy: A Cross-sectional 5 Years Rural Prevalence Study.

BACKGROUND: Epilepsy is one of the most common chronic neurological disorders. In children, it has long debilitating course and is associated with comorbidities including psychiatric comorbidity. To tackle this burden of comorbidities, we must know the extent of problem. Hence, there is a need for estimation of prevalence of psychiatry disorder in children with epilepsy. AIM: The present study was aimed at measuring the prevalence of various psychiatry disorders among children suffering from epilepsy. SETTINGS AND DESIGN: Cross-sectional chart review. METHODOLOGY: We reviewed case record files of all patients with a diagnosis of epilepsy in the age group of 9-17 years. Chart review was done for 5 years, May 1, 2007, to April 30, 2012. A total of 718 patients record were included in the study after satisfying inclusion criteria and excluding nonepilepsy diagnosis. STATISTICAL ANALYSIS: Statistics was done using Statistical Package for Social Sciences (SPSS 18.0). Descriptive statistics were used to calculate the result, Chi-square and Mann-Whitney U-test used wherever applicable. RESULTS: The prevalence of childhood psychiatric disorder among children with epilepsy found to be 31.2%. We also found that having a partial component (73.21%, n = 164) in seizure has more chances of psychopathology in comparison to generalized seizure (8.1%, n = 18). Among them, those having a partial component with generalization (66.96%, n = 150) had a greater prevalence of psychopathology. Mental retardation was most common psychiatric disorder among psychopathology followed by manic/depressive illness (unipolar) followed by unspecified nonorganic psychosis. CONCLUSION: From our study, we demonstrate the significant mental health needs of children with epilepsy. The evident high prevalence of psychiatry disorder emphasizes the need for psychopathology assessment and treatment as a part of any comprehensive epilepsy clinic.

Aberrant gamma band cortical sources and functional connectivity in adolescents with psychogenic non-epileptic seizures: A preliminary report.

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack clinically evident abnormal electrical activity in the brain. We aimed to assess resting gamma spectral power, current source distribution and functional connectivity in adolescents with PNES. Interictal, 32 channels electroencephalographic recording of 15 adolescents with PNES was compared with 10 matched healthy controls. Spectral power, current source distribution and lagged linear coherence were assessed. Statistically significant gamma spectral power, cortical sources and connectivity pattern was found in some brain areas. Region specific aberrant gamma activity and its relationship to psychopathology are discussed.

Effect of lithium on thyroid function in adolescents with mood disorder.

BACKGROUND: The purpose of the study was to determine thyroid gland volume and the frequency of thyroid dysfunction by using ultrasonography and laboratory parameters (TSH, T3, and T4) in long term lithium treated adolescent patients with mood disorder. METHODOLOGY: In a cross-sectional study, we performed ultrasonography and thyroid function test in 30 adolescent patients on long-term lithium treatment for mood disorder. Patients with adequate serum lithium levels for one year or more were taken for the study. Ultrasonography examinations of thyroid gland and thyroid function test were performed in these patients. Patients who were on other mood stabilizers were taken up as controls. RESULT: The thyroid stimulating hormone (TSH) levels and ultrasonographically measured thyroid volume were significantly higher in patients receiving lithium in comparison to patients with other mood stabilizers. A significant positive correlation was found between total thyroid volume and TSH levels. CONCLUSION: Adolescent mood disorder patients on long term lithium therapy have increased thyroid volume and isolated increases in serum TSH levels compared to those on other mood stabilizers.

Resting state theta band source distribution and functional connectivity in remitted schizophrenia.

Increased resting theta activity is one consistent observation occurring during all the phases of schizophrenia. However, the resting theta oscillations during the remission phase are yet unclear. We studied resting theta current source density and functional connectivity in remitted schizophrenia and compared with healthy controls. Significantly increased current source density was found in the dominant anterior cingulate cortex. Increased connectivity between the inferior parietal lobe bilaterally and between the left inferior parietal lobe and right middle frontal gyrus was also found. It may be concluded that schizophrenia patients have aberrant regional theta band current source density and functional connectivity even during remission.

The efficacy of cerebellar vermal deep high frequency (theta range) repetitive transcranial magnetic stimulation (rTMS) in schizophrenia: A randomized rater blind-sham controlled study.

Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic for schizophrenia. Treatment effects of rTMS have been variable across different symptom clusters, with negative symptoms showing better response, followed by auditory hallucinations. Cerebellum, especially vermis and its abnormalities (both structural and functional) have been implicated in cognitive, affective and positive symptoms of schizophrenia. rTMS to this alternate site has been suggested as a novel target for treating patients with this disorder. Hypothesizing cerebellar vermal magnetic stimulation as an adjunct to treat schizophrenia psychopathology, we conducted a double blind randomized sham controlled rTMS study. In this study, forty patients were randomly allocated (using block randomization method) to active high frequency (theta patterned) rTMS (n=20) and sham (n=20) groups. They received 10 sessions over 2 weeks. The Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) scores were assessed at baseline, after last session and at 4 weeks (2 weeks post-rTMS). We found a significantly greater improvement in the group receiving active rTMS sessions, compared to the sham group on negative symptoms, and depressive symptoms. We conclude that cerebellar stimulation can be used as an effective adjunct to treat negative and affective symptoms.

Subjective Symptoms in Euthymic Bipolar Disorder and Remitted Schizophrenia Patients: A Comparative Study.

BACKGROUND: Subjective experience means subtle, not yet psychotic abnormalities of experience that might be present during remitted phase and also in prodromal phase of schizophrenia and might be accurately efficient in identifying individuals at risk of eminent psychosis (Parnas et al., 2003). Apart from schizophrenic patients, bipolar patients also experience certain subjective symptoms in their euthymic state. They often experience subtle cognitive impairment and functional disturbances during their euthymic states. These subjective experiences may be related to distorted cognitive functions in these patients. These experiences include a great variety of cognitive dysfunction complaints about attention, perception, memory, thinking, language, movement, and emotion. OBJECTIVE: To measure the experience of subjective symptoms and compare them between euthymic bipolar and remitted schizophrenia patients. MATERIALS AND METHODS: Thirty euthymic bipolar patients and 30 remitted schizophrenia patients as per International Classification of Diseases Tenth Revision were selected for the purpose of the study. At first, sociodemographic data were collected. And then, the patients were assessed using the scales; positive and negative syndrome scale, Young Mania Rating Scale, Hamilton Depression Rating Scale, Symptom Checklist-90-Revised, and Frankfurt Complaint Questionnaire-24. RESULTS: Both the groups showed significant differences in terms of subjective symptoms. However, no significant correlation has been found between the objective psychopathology and subjective experience in the two groups. CONCLUSION: It can be suggested that the patients with schizophrenia show significantly higher subjective experience when compared with the patients of bipolar disorder.

Ultrasonographically Measured Change in Thyroid Status in Lithium Treated Adult Patients with Mood Disorder.

BACKGROUND: Lithium, which is frequently used in the treatment of mood disorder, can lead to various types of thyroid dysfunctions. Although clinical examination and biochemical assessment are fundamental to any thyroid work-up of lithium-treated patients, assessment findings vary widely depending on the investigator. Ultrasonographic measurement of thyroid volume has, therefore, been performed in lithium treatment populations and found to be a sensitive tool. AIM: We aimed to determine and compare thyroid gland volume using Ultrasonography and laboratory parameters, (thyroid-stimulating hormone [TSH], T3, and T4) in long-term lithium and other mood stabilizers treated patients with mood disorder. MATERIALS AND METHODS: In this cross-sectional study, we performed ultrasonography examinations and thyroid function test of 30 patients on lithium treatment and 30 patients on other mood stabilizers. RESULTS: The ultrasonographically measured thyroid volume was significantly increased in patients receiving lithium therapy as compared to the patients receiving other mood stabilizers. The total triiodothyronine (T3) was significantly increased with trends toward increased total thyroxine (T4) and decreased TSH in patients receiving lithium therapy as compared to the patients receiving other mood stabilizers. CONCLUSION: These results highlight the need of including ultrasonographic measurement of thyroid volume as a part of standard thyroid work-up before initiating lithium prophylaxis and during follow-up. Additional studies on the incidence and mechanism of lithium associated hyperthyroidism are needed.

Sustained Attention and Executive Functioning among Remitted Adolescents with Bipolar Disorder.

CONTEXT: Neuro-cognitive functions have not been extensively studied among young bipolar disorder patients. Researchers have found cognitive deficits in bipolar disorder and many have found such deficits even in euthymic states of the disorder but results are still inconclusive. AIM: To study sustained attention and executive functioning in remitted adolescents with bipolar disorder. SETTINGS AND DESIGN: Present study was a hospital-based cross-sectional study. MATERIALS AND METHODS: Twenty adolescents, aged 14-17 years with bipolar disorder, were selected for the study. Subjects were euthymic for at least 2 months. The performance of patients was matched with normal controls. Sustained attention was primarily measured by Letter Cancellation Test (LCT) and Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Stroop Colour Word Test were used to assess executive functions. Two groups differed significantly on level of education and thus multivariate linear model was used and education was put as a covariate. RESULTS: Results revealed that patients preformed less well than control. Significant poor performance was reported on LCT (omission scores), TMT, Stroop and WCST. CONCLUSION: The study confirmed previous findings stating that cognitive deficits like sustained attention and executive functions continue to be present in adolescent bipolar patients even in euthymic states.

Efficacy of Adjunctive High Frequency Repetitive Transcranial Magnetic Stimulation of Right Prefrontal Cortex in Adolescent Mania: A Randomized Sham-Controlled Study.

OBJECTIVE: To examine the efficacy of adjunctive right prefrontal high-frequency repetitive transcranial magnetic stimulation (rTMS) treatment in adolescent mania patients as compared to sham stimulation. METHODS: Twenty six right handed patients aged 12-17 years diagnosed with bipolar mania were randomized to receive daily sessions of active or sham rTMS (20 Hz, 110% of motor threshold, 20 trains, 10 s intertrain interval) over the right dorsolateral prefrontal cortex for 10 days. Mania was rated using Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) at baseline, and after 5th and 10th rTMS. RESULTS: For YMRS scores, repeated measures analysis of variance (ANOVA) showed a significant main effect (F=44.49, degree of freedom [df]=1.2/29.29, p<0.001, Greenhouse-Geisser corrected, effect size η(2)=0.65), but the interaction effect was not significant (F=0.03, df=1.2/29.29, p=0.912, Greenhouse-Geisser corrected). For CGI-Severity, repeated measures ANOVA showed a significant main effect (F=24.49, df=1.42/34.21, p<0.001, Greenhouse-Geisser corrected, effect size η(2)=0.51), but the interaction effect was not significant (F=0.06, df=1.2/29.29, p=0.881, Greenhouse-Geisser corrected). CONCLUSION: High-frequency right prefrontal rTMS was found to be ineffective as add-on to standard pharmacotherapy in adolescent mania.

Tourette syndrome and bipolar disorder: unique problems with pediatric comorbidity.

Tourette syndrome and bipolar disorder are frequent comorbidities in pediatric age group. They provide a clinician with certain unique challenges. While on one hand the tics mask manifestation of affective symptomatology, the latter makes it difficult to elicit tics with certainty. Data suggest that they might share genetic and neurobiological basis and this is currently an area of extensive research. These clinical and biological overlaps provide grey areas in our understanding, which not only complicates the diagnosis, but also poses problems with management.

Gamma activity model for treatment-resistant bipolar psychotic mania.

OBJECTIVES: The objective was to investigate the effect of clozapine on spontaneous gamma activity in treatment-resistant bipolar psychotic mania. METHODS: Patients with treatment-resistant (TR) bipolar psychotic mania on clozapine monotherapy and nontreatment-resistant bipolar psychotic mania patients receiving lithium were prospectively studied for 6 weeks on severity of psychopathology and 30-49 Hz gamma spectral power. RESULTS: Spectral power significantly increased in the lithium group and decreased in the clozapine group; no within group significant difference found. CONCLUSIONS: We propose a model highlighting the role of gamma spectral power and modulations of GABAergic neurotransmission in TR bipolar psychotic mania.