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Biomedical subjects

Esa Leinonen

Publications and source records attributed to Esa Leinonen.

At least 19 recordsLinked to original sources
PubMed2007

Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not associated with response to electroconvulsive therapy in major depressive disorder.

The aim of the present study was to examine an association of brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T and the response to electroconvulsive therapy (ECT) in major depressive disorder (MDD). The study group consisted of 119 patients consecutively admitted for ECT in the Department of Psychiatry, Tampere University Hospital. All patients fulfilled the diagnostic criteria of DSM-IV for MDD. ECT was administered three times a week with a brief pulse constant current device. The Montgomery and Asberg Depression Rating Scale (MADRS) was used as an outcome measure of depression. Genotyping was performed using fluorescent allele-specific TaqMan probes. No association between either G196A or C270T and the response to ECT was found in the whole population. There were no significant differences in responses between men and women or between psychotic and non-psychotic patients. However, within subgroups such as in psychotic and in late-onset depression CC genotype of C270T may predict good response. BDNF may not be associated with response to ECT in general, but some association in subgroups may exist.

Age of Onset↗
PubMed2006

Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia.

The aim of this study was to investigate the relationship between the functional C957T single-nucleotide polymorphism of the dopamine D2 receptor (DRD2) gene and the risk for schizophrenia. We therefore conducted a case-control association study of 188 Finnish schizophrenia patients meeting the DSM-IV criteria and 384 healthy controls. The 5' nuclease assay (TaqMan) was used to determine genotypes. A greater proportion of patients with schizophrenia than healthy controls were C-allele carriers (odds ratio 1.5, 95% confidence interval (CI) 1.0-2.3, P=0.05). Our results are in agreement with an earlier association study suggesting that the C957T C-allele plays a role in the genetic vulnerability for schizophrenia and support the involvement of the DRD2 gene in schizophrenia pathogenesis.

Adult↗
PubMed2006

Use of antipsychotics among nonagenarian residents in long-term institutional care in Finland.

BACKGROUND: There is a paucity of information about the use of antipsychotic medication in long-term care, especially among the oldest-old residents. OBJECTIVE: To analyse the factors associated with the use of antipsychotic medication among nonagenarian residents in long-term institutional care. DESIGN: A retrospective study was designed from cross-sectional data, gathered in the period 1 January 2003 to 30 June 2003, in Finland. Data were extracted from the Resident Assessment Instrument database, based on Minimum Data Set 2.0 assessments. SETTING: Data were provided by 23 hospital-based institutions and 43 residential homes. SUBJECTS: Residents aged >or=90 years were included, consisting of 1,334 resident assessments. RESULTS: Almost a third of the residents received one or more antipsychotic medication. In the logistic regression analysis, factors associated with the use of antipsychotics among nonagenarian residents were as follows: socially inappropriate or disruptive behavioural symptoms [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.36-2.54], concomitant anxiolytic medication (OR 1.83, 95% CI 1.39-2.42), recurring anxious complaints (OR 1.61, 95% CI 1.17-2.22), recurring physical movements (OR 1.43, 95% CI 1.08-1.91) and unsettled relationships (OR 1.35, 95% CI 1.15-1.57). A good sense of initiative or involvement was significantly less likely to be associated with antipsychotics (OR 0.86, 95% CI 0.80-0.94). There were no associations between any psychiatric diagnoses or symptoms and the use of antipsychotics. CONCLUSIONS: Antipsychotic medication use in nonagenarians in long-term institutions was common and seemed in many cases to be associated with residents' negative attitudes to others. Querulous residents received antipsychotics more commonly than those with good social skills. Clearly defined indications may not be fulfilled in many cases, and an evaluation of treatment may be lacking. These may indicate that in Finland, there could be a considerable gap between antipsychotic medication recommendations and actual clinical practice.

Aged, 80 and over↗
PubMed2006

Use of antipsychotic medications among elderly residents in long-term institutional care: a three-year follow-up.

OBJECTIVE: To analyse the use of antipsychotic medications, change over time and associated factors in a three-year follow-up among elderly residents in long-term institutional care. DESIGN: Retrospective study was designed with three identical cross-sectional samples originating from the same long-term care facilities, and collected 1 July to 31 December in 2001, 2002 and 2003, in Finland. These were extracted from the Resident Assessment Instrument (RAI) database, based on Minimum Data Set (MDS) assessments. SETTING: Of the data providers 16 were hospital-based institutions and 25 residential homes. PARTICIPANTS: Each of the data sets included 3,662-3,867 resident assessments. RESULTS: The prevalence use of one or more antipsychotic decreased from 42% in 2001 to 39% in 2003. The overall confounder-adjusted decrease in antipsychotic use was not statistically significant. However, the use of antipsychotics decreased among residents who had wandering as a behavioural problem (OR 0.79, 95% CI 0.63-0.99) and increased among residents with concomitant use of anxiolytic medications (OR 1.23, 95% CI 1.03-1.48). CONCLUSIONS: The use of antipsychotic medications among residents in long-term institutional care was common and the caring patterns were quite stable during the observation period. Adequate indications may not have been achieved in all cases. More attention should be paid to the appropriate use of antipsychotics in this frail population.

Age Factors↗
PubMed2005

Changes in plasma amino acids after electroconvulsive therapy of depressed patients.

There are indications that mood disorders may be related to perturbations in the amino acid transmitters. The amino acids may thus be targets of treatment of depression. The purpose of this pilot study was to measure the acute effects of a single administration of electroconvulsive therapy (ECT) on the plasma levels of amino acids in depressed patients. ECT was administered to 10 patients with major depressive disorder. Altogether 23 plasma amino acids were analyzed before and at 2, 6, 24 and 48 h after ECT. The levels of glutamate and aspartate increased at 6 h after ECT compared with the baseline. Also the levels of total tryptophan increased 2-24 h after ECT. There were also elevations in other amino acids at 6 and 24 h. The levels of gamma-aminobutyric acid (GABA) decreased at 2 h. In this study the acute effects of single ECT were associated with changes in the levels of glutamate, aspartate, GABA, tryptophan and some other amino acids. The preliminary data suggest that the therapeutic effects of ECT in depression may be due to mechanisms involving these amino acid transmitters.

Adult↗
PubMed2005

The apolipoprotein E polymorphism is not associated with response to electroconvulsive therapy in major depressive disorder.

The apolipoprotein E (APOE) polymorphism is associated with neurodegenerative diseases. Its role regarding psychiatric disorders is controversial. It has been suggested to affect antidepressant treatment response and response to electroconvulsive therapy (ECT). In the present study, the association between APOE polymorphism and response to ECT in 119 patients with major depressive disorder was investigated. Moreover, a relation between APOE polymorphism and the age of onset of depression as well as the cognitive outcome of ECT was studied. In the whole population, no association was found between APOE polymorphism and response to ECT. However, in nonpsychotic patients, the epsilon2 allele tended to be more frequent in responders than nonresponders. Earlier onset of depression was observed in the patients with epsilon4 allele in late-life depression. There was no association between the APOE genotype and the cognitive change caused by ECT in the population as a whole. In women, however, epsilon2 allele may play a protective and epsilon4 allele a deleterious role in cognition during ECT.

Adult↗
PubMed2005

Effect of anticholinergics in preventing acute deterioration in patients undergoing abrupt clozapine withdrawal.

BACKGROUND: The most serious adverse effect of clozapine, agranulocytosis, was described for the first time in Finland in 1975. It caused the immediate withdrawal of clozapine from the market and immediate discontinuation of this medication in all patients. It is now known that abrupt withdrawal of clozapine may cause a rapid deterioration in psychotic symptoms. OBJECTIVE: The aim of this retrospective study was to investigate the effect of abrupt clozapine withdrawal on psychiatric patients, and to examine whether anticholinergic drugs are effective in preventing acute deterioration. MATERIALS AND METHODS: We reviewed the hospital case records from Pitkäniemi Psychiatric Hospital, Tampere, Finland, of the 28 patients with schizophrenia who had been receiving clozapine and from whom it was abruptly withdrawn due to the withdrawal of the drug from the market in the summer of 1975. We assessed the incidence of deterioration and whether or not patients in whom this occurred were receiving anticholinergic drugs. RESULTS: We found a rapid deterioration after clozapine withdrawal in almost half (46.4%; n = 13) of the patients. Patients receiving anticholinergic drugs (such as antiparkinsonians, tricyclic antidepressants and antipsychotics with anticholinergic properties) were significantly less likely to deteriorate than those not receiving these drugs (21.4% vs 71.4%, p = 0.008). The condition of the patients who deteriorated was poor for up to 1 month after discontinuation, but had improved slightly by the end of 1975. CONCLUSION: Anticholinergic medication should be considered for preventing possible symptom deterioration when clozapine is abruptly discontinued.

Adolescent↗
PubMed2004

Interaction of tumor necrosis alpha - G308A and epidermal growth factor gene polymorphisms in early-onset schizophrenia.

The study population comprised 94 Finnish patients with DSM-IV diagnosis of schizophrenia. The patients were placed into two subgroups according to medication response to conventional neuroleptics. The aim of the study was to examine the frequency of tumor necrosis factor -308 (G > A) polymorphism in these patients and their 98 control subjects who were age- and gender-matched blood donors. Associations between TNFalpha -308 polymorphism alone and between the interaction of TNFalpha and epidermal growth factor gene polymorphisms, and medication response and age at onset of schizophrenia were also studied. The frequencies of TNFalpha A-allele were 11.7 % in patients and 12.8% in controls. The difference was not significant (p = 0.75). TNFalpha -308 polymorphism was not associated with medication response. However, patients with EGF AA and TNFalpha AG/AA genotype had a lower age at onset of schizophrenia compared with the rest of the patients not having this combination (20.0 years, 3.3 vs. 30.2 years, 10.1 mean + SD; p < 0.001). The results support earlier findings according to which TNFalpha polymorphism is not associated with the incidence of schizophrenia. On the other hand, the role of cytokines in schizophrenia may involve genetic interactions predisposing early onset of illness.

Adult↗
PubMed2004

Neuregulin genotype and medication response in Finnish patients with schizophrenia.

Neuregulin 1 is involved both in neurodevelopment and neurotransmitter mechanisms in the brain. There is evidence of an association between neuregulin 1 genotype and schizophrenia. We compared neuregulin 1 genotypes in patients with schizophrenia (n=94) and control subjects (n=395) of Finnish origin by using one SNP (SNP8NRG221533) as a genetic marker. We also analyzed NRG1 genotype with regard to age at onset and between responders and non-responders to conventional antipsychotics. The NRG1 genotype or allele frequencies showed similar distributions between patient and control groups. Age at onset was not associated with NRG1 genotype. The TT genotype was overrepresented in the non-responders group compared with the responders (p=0.013). Further studies are needed to ascertain the significance of neuregulin genotype in medication response to schizophrenia.

Adult↗
PubMed2004

Apolipoprotein E polymorphism is associated with age of onset in schizophrenia.

The aims of the study were to investigate the relationship between Apolipoprotein E (APOE) polymorphism, risk of schizophrenia, treatment response to conventional anti-psychotics, and age of onset in schizophrenia. The sample comprised 94 Finnish patients with a DSM-IV diagnosis of schizophrenia. Forty-three of the patients were good responders to conventional anti-psychotics and 51 were classified as non-responders. The control group consisted of 98 healthy blood donors. The APOE allele frequencies (epsilon 2, epsilon 3, and epsilon 4) were 4.8, 72.3, and 22.9% in patients and 7.1, 75.0, and 17.9 in controls. None of the differences between groups were statistically significant. No association between treatment response and APOE genotype was found. Patients with APOE epsilon 4/epsilon 4 genotype had a markedly lower age of onset compared with rest of the sample (p=0.0015), which remained significant when controlling for gender (p=0.02). There was an increasing linear trend between the number of epsilon 3 alleles (0, 1, or 2) and age of onset in schizophrenia (p=0.08). An inverse trend was found between the number of epsilon 4 alleles and age of onset (p=0.07). No relationship between APOE polymorphism and risk for schizophrenia was found. APOE epsilon 4/epsilon 4 genotype may be associated with early onset schizophrenia. APOE epsilon 3 allele may function protectively in later onset in this disease.

Adult↗
PubMed2004

Association of EGF polymorphism with schizophrenia in Finnish men.

Some recent data suggest that epidermal growth factor (EGF) protein levels are altered in the brain of schizophrenic patients. In addition, a novel polymorphism of the EGF gene is associated with enhanced production of EGF in vitro. We conducted a retrospective study to explore the impact of EGF polymorphism on factors associated with schizophrenia. The sample consisted of 94 patients with schizophrenia who had either responded to treatment with conventional neuroleptics or who were considered non-responders. The control sample consisted of 98 blood donors. In our sample, the G allele was associated with schizophrenia in male patients (OR = 3.594 (95% CI 1.347-9.591), p = 0.008). The G allele was also associated with a later age at onset in male patients with schizophrenia. However, no association was found between treatment response and EGF polymorphism.

Adult↗
PubMed2004

Elderly patients with major depressive disorder and delusional disorder are at increased risk of subsequent dementia.

All the patients (n=150) admitted to psychogeriatric clinic during a 1-year period were followed up until their death or for 10 years. Fifteen of these were lost during the 10-year follow-up. Thus, follow-up data were available for 135 patients. Twenty-four of these fulfilled at baseline the DSM-III-R diagnostic criteria of major depressive disorder and 18 of delusional disorder after careful medical examination and neuropsychological tests to eliminate organic causes. In the follow-up, the diagnoses were gathered from the death certificates of those patients who died during the 10-year period and all of the patients alive at the end of the study were interviewed to assess their mental state. Six out of the 24 (25%) patients with major depressive and five out of 18 (28%) patients with delusional disorder developed clear organic dementia before death or within 10 years (mean follow-up time 6.7 years). This is approximately double the expected incidence in the general population of that age. The gender, age at index admission, the baseline Mini Mental State Examination scores or findings in computer tomography did not contribute to the risk of dementia. Psychogeriatric patients admitted due to major mental disorder may have an increased risk of organic dementia in the near future.

Aged↗
PubMed2004

Interaction between NOTCH4 and catechol-O-methyltransferase genotypes in schizophrenia patients with poor response to typical neuroleptics.

OBJECTIVE: In this study we attempted to show that the interaction between NOTCH4 and catechol-O-methyltransferase (COMT) polymorphism predicts the response to typical neuroleptics in schizophrenia. Our sample consisted of 94 Finnish patients with DSM-IV schizophrenia and 98 controls. METHODS: Several studies have connected COMT and NOTCH4 genes to schizophrenia. We have previously shown that COMT polymorphism is significantly associated with treatment response in schizophrenia. NOTCH4 SNP2 polymorphism has been associated with age of onset in schizophrenia, but there is also a trend that this polymorphism may predict response to typical neuroleptics. In the present sample, there is a strong gene-gene interaction between these genes (P = 0.003) and they have additive effect in treatment response. RESULTS: Patients carrying both NOTCH4 C/C genotype and COMT low/low genotype, had more than ten times higher risk of being a non-responder than responder to treatment with typical neuroleptics [OR = 10.25 (95% CI 2.21-47.53), P < 0.001]. This combination of genotypes is also more common in patients considered non-responders than in controls [OR = 3.00 (95% CI 1.33-6.76), P = 0.007]. CONCLUSION: Our results suggest that an interaction between COMT and NOTCH4 genotypes may predict the treatment response to typical neuroleptics in patients with schizophrenia.

Antipsychotic Agents↗
PubMed2004

One-year outcome of elderly inpatients with major depressive disorder treated with ECT and antidepressants.

We report the acute response and outcome in 1-year follow-up of 51 elderly depressive inpatients with major depressive disorder treated with electroconvulsive therapy (ECT) (n = 30) and/or antidepressant therapy (n = 21). The patients were assessed at admission, at discharge, and after 1 year according to the Montgomery and Asberg Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global Impression Scale. The acute response was good. Montgomery and Asberg Depression Rating Scale total scores diminished significantly during index hospitalization within both groups (from 31.6 +/- 8.5, to 8.1 +/- 6.0 in the ECT group and from 28.5 +/- 5.4 to 13.4 +/- 10.6 in the antidepressant group). The 1-year rehospitalization rate for the entire group, however, was 21 of 51 patients (41%), 13 of 30 patients (43%) in the ECT group, and 8 of 21 (38%) in the antidepressant group. Six of 13 patients in the ECT group and 1 of 8 patients in the antidepressant group were rehospitalized during the first month after discharge. The results suggest a good acute therapeutic response to both ECT and antidepressive therapy in elderly patients with MDD. The major finding in this study was the relatively high rehospitalization rate, which emphasizes the need for careful follow-up of the elderly patients who have recovered from a depressive episode.

Aged↗
PubMed2003

Dopamine receptor D2 -141C Insertion/Deletion polymorphism in a Finnish population with schizophrenia.

We examined the occurrence of the -141C Ins/Del polymorphism in 93 Finnish patients with schizophrenia. In comparison with previous studies with Japanese and Caucasian populations, the incidence of this polymorphism was unexpectedly low. The findings suggest that the frequency of the -141C Ins/Del polymorphism is lower in Northern Europe compared to other Caucasian and Japanese populations.

Alleles↗
PubMed2003

Interaction between angiotensin-converting enzyme and catechol-O-methyltransferase genotypes in schizophrenics with poor response to conventional neuroleptics.

Angiotensin-converting enzyme (ACE) modulates dopamine turnover in the brain and catechol-O-methyltransferase (COMT) enzyme is an important agent in the metabolic inactivation of dopamine and norepinephrine. Functional polymorphism in the COMT and ACE genes causes variation in enzyme activities. We investigated the relationship of COMT and ACE gene polymorphism with response to conventional neuroleptic treatment in schizophrenia. In this study population we had earlier detected that COMT genotype is associated with unsatisfactory drug response. A total of 94 schizophrenic patients were evaluated either as responders (n=43) or non-responders (n=51). The responders had experienced a fair and steady response to conventional neuroleptics. The non-responders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age- and gender-matched blood donors. Genotyping of the COMT and ACE genes was performed by polymerase chain reaction. The risk of having both low activity COMT and high activity ACE genotypes was over 10 times higher (odds ratio=10.89, 95%CI 1.14-103.98, P=0.04) in the non-responders compared to responders. ACE genotype alone did not differ between any groups. This finding may suggest a possible interaction with low activity COMT and high activity ACE genotype in association with poor response to conventional neuroleptics.

Adult↗
PubMed2003

Catechol-O-methyltransferase and monoamine oxidase A genotypes and drug response to conventional neuroleptics in schizophrenia.

Biogenic amine synthesis and degradation are involved in the pathogenesis of schizophrenia. Catechol-O-methyltransferase and monoamine oxidase enzymes are important agents in the metabolic inactivation of these neurotransmitters (ie, dopamine, serotonin, and norepinephrine). Functional polymorphism in the catechol-O-methyltransferase and monoamine oxidase A genes causes variation in enzyme activities. We investigated the relationship of catechol-O-methyltransferase Val158Met and monoamine oxidase A promoter repeat polymorphism with response to conventional neuroleptic treatment in schizophrenia.Ninety-four schizophrenic patients formed 2 different study populations. The responders had experienced a fair and steady response to conventional neuroleptics. The nonresponders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age-matched and gender-matched blood donors. Genotyping of the catechol-O-methyltransferase and monoamine oxidase A genes was performed by polymerase chain reaction.Forty-three percent of the nonresponders had a low activity catechol-O-methyltransferase genotype compared with 16% of the responders (P = 0.009). Monoamine oxidase A genotype alone did not differ significantly between the groups. Moreover, the risk of having both low-activity catechol-O-methyltransferase and monoamine oxidase A genotypes was over 6 times more common (odds ratio = 6.16, P = 0.03) in the nonresponders compared with responders. The whole population of patients with schizophrenia did not differ from the controls.The low-activity catechol-O-methyltransferase genotype may be associated with unsatisfactory drug response to conventional neuroleptics or alternatively be involved in a subset of schizophrenics. The role of monoamine oxidase A genotype seems to be additive in this respect.

Adult↗