Jari Tiihonen - Academia.edu (original) (raw)

Papers by Jari Tiihonen

American journal of psychotherapy, 2005

We explored the outcome of psychodynamic psychotherapy of a female patient with major depression ... more We explored the outcome of psychodynamic psychotherapy of a female patient with major depression using clinical evaluation and serotonin transporter (SERT) binding assessed with [123I]nor-beta-CIT SPECT. The psychotherapy process was analyzed with special emphasis on the change that was recognized in the dreaming process. The activation of the dream screen in transference seemed to form a turning point during the psychotherapy. Normalization of SERT binding at the midbrain level was found on 12-month follow-up. Major alleviation of depressive symptoms assessed by rating scales was evident only six months after SERT normalization.

Schizophrenia Bulletin

Background and Hypothesis Optimal doses of most antipsychotics in the maintenance treatment of sc... more Background and Hypothesis Optimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study Methods We studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study Results Among the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6–<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68–0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had t...

Brain Sciences, 2021

The purpose of this study was to explore the association between cognition and hazardous drinking... more The purpose of this study was to explore the association between cognition and hazardous drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognition is more or less compromised in schizophrenia, and schizoaffective disorder and alcohol use might aggravate this phenomenon. The study population included 3362 individuals from Finland with diagnoses of schizophrenia or schizoaffective disorder. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol use disorder (AUD) diagnoses were obtained from national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: The Five-Choice Serial Reaction Time Task (5-CSRTT) or the reaction time (RT) test and the Paired Associative Learning (PAL) test. The association between alcohol use and the RT and PAL tests was analyzed with log-linear regress...

Schizophrenia Research, 2021

Psychological Medicine, 2020

Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of sch... more Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of schizophrenia (SCZ). We differentiated astrocytes from induced pluripotent stem cells of monozygotic twins discordant for SCZ, and found sex-specific gene expression and signaling pathway alterations related particularly to inflammation and synaptic functions. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins, and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in demyelination, synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Al...

Molecular Psychiatry, 2019

A correction to this paper has been published and can be accessed via a link at the top of the pa... more A correction to this paper has been published and can be accessed via a link at the top of the paper.

Molecular Psychiatry, 2019

Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general po... more Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general population, and 10–30% among incarcerated criminal offenders. Although the heritability of severe antisocial behavior is up to 50%, the genetic background is unclear. The underlying molecular mechanisms have remained unknown but several previous studies suggest that abnormal glucose metabolism and opioidergic neurotransmission contribute to violent offending and psychopathy. Here we show using iPSC-derived cortical neurons and astrocytes from six incarcerated extremely antisocial and violent offenders, three nonpsychopathic individuals with substance abuse, and six healthy controls that there are robust alterations in the expression of several genes and immune response-related molecular pathways which were specific for psychopathy. In neurons, psychopathy was associated with marked upregulation of RPL10P9 and ZNF132, and downregulation of CDH5 and OPRD1. In astrocytes, RPL10P9 and MT-RNR2 ...

Translational Psychiatry, 2015

International clinical psychopharmacology, 2017

The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associa... more The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associated with incident benzodiazepine and related drug (BZDR) use among community-dwelling individuals with Alzheimer's disease (AD). Data from the MEDALZ cohort including all community-dwelling persons newly diagnosed with AD between 2005 and 2011 in Finland were utilized. Incident BZDR users were identified with a 1-year washout period for previous use. Persons with a previous stroke were excluded, resulting in a final study sample of 45 050 individuals. Incident any, ischemic, and hemorrhagic strokes were identified from the Hospital Discharge and Causes of Death registers. The risk of stroke between time on BZDRs was compared with nonuse time with Cox proportional hazard models. During the follow-up, 21.9% (N=9879) of persons started BZDR use. Compared with nonuse, BZDR use was associated with an increased risk of any stroke [adjusted hazard ratio (aHR): 1.21; 95% confidence interval ...

The Journal of clinical psychiatry, 2017

To study whether antipsychotic use is associated with a risk of hip fracture among individuals wi... more To study whether antipsychotic use is associated with a risk of hip fracture among individuals with Alzheimer's disease and to compare the risk according to the duration of use and the 2 most frequently used antipsychotics. The MEDALZ (Medication and Alzheimer's disease) cohort consisted of community-dwelling Finnish persons with clinically verified diagnoses of Alzheimer's disease, including 70,718 persons newly diagnosed according to NINCDS-ADRDA and DSM-IV criteria between 2005 and 2011. Antipsychotic use was modeled from prescription register data, and hip fractures (ICD-10 S72.0-72.2) were identified from the Hospital Discharge Register. The incidence of hip fractures was compared between new users and nonusers of antipsychotics, among various time durations of antipsychotic use, and between quetiapine users and risperidone users. Antipsychotic use versus nonuse was associated with an increased risk of hip fractures (adjusted hazard ratio [HR] = 1.54; 95% CI, 1.39-1...

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 10, 2017

Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) ar... more Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common. We obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland (2005-2011) from the Medication use and Alzheimer disease (MEDALZ) cohort, which incorporates national registry data on prescriptions, reimbursement, hospital discharges and causes of death. Incident users of benzodiazepines and Z-drugs were identified using a 1-year washout period and matched with nonusers using propensity scores. The association with hospital admission or death due to pneumonia was analyzed with the Cox proportional hazards model and adjusted for use of other psychotropic drugs in a time-dependent manner. Among 49 484...

Pharmacoepidemiology and drug safety, Jan 29, 2017

To assess whether a "drugome-wide" screen with case-crossover design is a feasible appr... more To assess whether a "drugome-wide" screen with case-crossover design is a feasible approach for identifying candidate drugs and drug-drug interactions. All community-dwelling residents of Finland who received a clinically verified Alzheimer disease diagnosis in 2005 to 2011 and experienced incident hip fracture (HF) afterwards (N = 4851). Three scenarios were used to test the sensitivity of this approach (1) hazard period 0 to 30 and control period 31 to 61 days before HF, (2) hazard period 0 to 30 and control period 336 to 366 days before HF, and (3) hazard period 0 to 14 and control period 16 to 30 days before HF. Nine, 44, and 5 drugs were associated with increased HF risk and 8, 23, and 4 with decreased risk in scenarios 1, 2, and 3, respectively. Six drugs were identified with scenario 1 only and 54 and 1 with scenarios 2 and 3, respectively. Only six drugs (metoprolol, simvastatin, trimethoprim, codeine combinations, fentanyl, and paracetamol) were associated with HF...

Journal of Preventive Medicine and Public Health, 2016

Psychiatry research, Jan 28, 2015

Current risk assessment tools have a moderate predicting value for violence. Their power may be e... more Current risk assessment tools have a moderate predicting value for violence. Their power may be enhanced with certain biological indicators, which may serve as predictors of recidivistic violence itself. The aim of our study was to determine the strength of serum insulin levels to predict violence, and compare these results with those from the Revised Psychopathy Checklist (PCL-R). The study population consisted of 105 Finnish alcoholics who were severely violent offenders, recruited from 1991 to 1998. After exclusion, 75 cases were followed until March 2008, or until a new offense was registered. Cox regression analysis was used to evaluate the risk of recidivism. The age and weight adjusted effect of insulin to recidivism risk showed a 7.2% increase for each International Unit (IU), or 19% for the mean difference (2.5IU) between recidivists and non-recidivist, which corresponds to a medium effect size (Cohen׳s d=0.46). Adjusting the insulin model with PCL-R factor 1 enhanced the p...

Molecular psychiatry, Jan 28, 2014

In developed countries, the majority of all violent crime is committed by a small group of antiso... more In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal viole...

American journal of psychotherapy, 2011

The perceptions of patients (n = 25) and their therapists about psychodynamic psychotherapy for d... more The perceptions of patients (n = 25) and their therapists about psychodynamic psychotherapy for depression were assessed during the first treatment year using 23 scales. Patients and therapists independently evaluated the impact of depression on the therapeutic experience of the patients. The estimations of the impact of depression by the patients and therapists were concordant in the majority of the subjects, reflecting mutual tuning and a working alliance. The roles of affects and frustrating subjects in the treatment relationship were evaluated as significantly different by the patients and the therapists. The results highlight the importance of working on the expression of affects in the psychotherapy of depression.

American journal of psychotherapy, 2005

We explored the outcome of psychodynamic psychotherapy of a female patient with major depression ... more We explored the outcome of psychodynamic psychotherapy of a female patient with major depression using clinical evaluation and serotonin transporter (SERT) binding assessed with [123I]nor-beta-CIT SPECT. The psychotherapy process was analyzed with special emphasis on the change that was recognized in the dreaming process. The activation of the dream screen in transference seemed to form a turning point during the psychotherapy. Normalization of SERT binding at the midbrain level was found on 12-month follow-up. Major alleviation of depressive symptoms assessed by rating scales was evident only six months after SERT normalization.

Schizophrenia Bulletin

Background and Hypothesis Optimal doses of most antipsychotics in the maintenance treatment of sc... more Background and Hypothesis Optimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study Methods We studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study Results Among the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6–<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68–0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had t...

Brain Sciences, 2021

The purpose of this study was to explore the association between cognition and hazardous drinking... more The purpose of this study was to explore the association between cognition and hazardous drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognition is more or less compromised in schizophrenia, and schizoaffective disorder and alcohol use might aggravate this phenomenon. The study population included 3362 individuals from Finland with diagnoses of schizophrenia or schizoaffective disorder. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol use disorder (AUD) diagnoses were obtained from national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: The Five-Choice Serial Reaction Time Task (5-CSRTT) or the reaction time (RT) test and the Paired Associative Learning (PAL) test. The association between alcohol use and the RT and PAL tests was analyzed with log-linear regress...

Schizophrenia Research, 2021

Psychological Medicine, 2020

Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of sch... more Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of schizophrenia (SCZ). We differentiated astrocytes from induced pluripotent stem cells of monozygotic twins discordant for SCZ, and found sex-specific gene expression and signaling pathway alterations related particularly to inflammation and synaptic functions. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins, and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in demyelination, synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Al...

Molecular Psychiatry, 2019

A correction to this paper has been published and can be accessed via a link at the top of the pa... more A correction to this paper has been published and can be accessed via a link at the top of the paper.

Molecular Psychiatry, 2019

Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general po... more Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general population, and 10–30% among incarcerated criminal offenders. Although the heritability of severe antisocial behavior is up to 50%, the genetic background is unclear. The underlying molecular mechanisms have remained unknown but several previous studies suggest that abnormal glucose metabolism and opioidergic neurotransmission contribute to violent offending and psychopathy. Here we show using iPSC-derived cortical neurons and astrocytes from six incarcerated extremely antisocial and violent offenders, three nonpsychopathic individuals with substance abuse, and six healthy controls that there are robust alterations in the expression of several genes and immune response-related molecular pathways which were specific for psychopathy. In neurons, psychopathy was associated with marked upregulation of RPL10P9 and ZNF132, and downregulation of CDH5 and OPRD1. In astrocytes, RPL10P9 and MT-RNR2 ...

Translational Psychiatry, 2015

International clinical psychopharmacology, 2017

The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associa... more The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associated with incident benzodiazepine and related drug (BZDR) use among community-dwelling individuals with Alzheimer's disease (AD). Data from the MEDALZ cohort including all community-dwelling persons newly diagnosed with AD between 2005 and 2011 in Finland were utilized. Incident BZDR users were identified with a 1-year washout period for previous use. Persons with a previous stroke were excluded, resulting in a final study sample of 45 050 individuals. Incident any, ischemic, and hemorrhagic strokes were identified from the Hospital Discharge and Causes of Death registers. The risk of stroke between time on BZDRs was compared with nonuse time with Cox proportional hazard models. During the follow-up, 21.9% (N=9879) of persons started BZDR use. Compared with nonuse, BZDR use was associated with an increased risk of any stroke [adjusted hazard ratio (aHR): 1.21; 95% confidence interval ...

The Journal of clinical psychiatry, 2017

To study whether antipsychotic use is associated with a risk of hip fracture among individuals wi... more To study whether antipsychotic use is associated with a risk of hip fracture among individuals with Alzheimer's disease and to compare the risk according to the duration of use and the 2 most frequently used antipsychotics. The MEDALZ (Medication and Alzheimer's disease) cohort consisted of community-dwelling Finnish persons with clinically verified diagnoses of Alzheimer's disease, including 70,718 persons newly diagnosed according to NINCDS-ADRDA and DSM-IV criteria between 2005 and 2011. Antipsychotic use was modeled from prescription register data, and hip fractures (ICD-10 S72.0-72.2) were identified from the Hospital Discharge Register. The incidence of hip fractures was compared between new users and nonusers of antipsychotics, among various time durations of antipsychotic use, and between quetiapine users and risperidone users. Antipsychotic use versus nonuse was associated with an increased risk of hip fractures (adjusted hazard ratio [HR] = 1.54; 95% CI, 1.39-1...

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 10, 2017

Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) ar... more Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common. We obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland (2005-2011) from the Medication use and Alzheimer disease (MEDALZ) cohort, which incorporates national registry data on prescriptions, reimbursement, hospital discharges and causes of death. Incident users of benzodiazepines and Z-drugs were identified using a 1-year washout period and matched with nonusers using propensity scores. The association with hospital admission or death due to pneumonia was analyzed with the Cox proportional hazards model and adjusted for use of other psychotropic drugs in a time-dependent manner. Among 49 484...

Pharmacoepidemiology and drug safety, Jan 29, 2017

To assess whether a "drugome-wide" screen with case-crossover design is a feasible appr... more To assess whether a "drugome-wide" screen with case-crossover design is a feasible approach for identifying candidate drugs and drug-drug interactions. All community-dwelling residents of Finland who received a clinically verified Alzheimer disease diagnosis in 2005 to 2011 and experienced incident hip fracture (HF) afterwards (N = 4851). Three scenarios were used to test the sensitivity of this approach (1) hazard period 0 to 30 and control period 31 to 61 days before HF, (2) hazard period 0 to 30 and control period 336 to 366 days before HF, and (3) hazard period 0 to 14 and control period 16 to 30 days before HF. Nine, 44, and 5 drugs were associated with increased HF risk and 8, 23, and 4 with decreased risk in scenarios 1, 2, and 3, respectively. Six drugs were identified with scenario 1 only and 54 and 1 with scenarios 2 and 3, respectively. Only six drugs (metoprolol, simvastatin, trimethoprim, codeine combinations, fentanyl, and paracetamol) were associated with HF...

Journal of Preventive Medicine and Public Health, 2016

Psychiatry research, Jan 28, 2015

Current risk assessment tools have a moderate predicting value for violence. Their power may be e... more Current risk assessment tools have a moderate predicting value for violence. Their power may be enhanced with certain biological indicators, which may serve as predictors of recidivistic violence itself. The aim of our study was to determine the strength of serum insulin levels to predict violence, and compare these results with those from the Revised Psychopathy Checklist (PCL-R). The study population consisted of 105 Finnish alcoholics who were severely violent offenders, recruited from 1991 to 1998. After exclusion, 75 cases were followed until March 2008, or until a new offense was registered. Cox regression analysis was used to evaluate the risk of recidivism. The age and weight adjusted effect of insulin to recidivism risk showed a 7.2% increase for each International Unit (IU), or 19% for the mean difference (2.5IU) between recidivists and non-recidivist, which corresponds to a medium effect size (Cohen׳s d=0.46). Adjusting the insulin model with PCL-R factor 1 enhanced the p...

Molecular psychiatry, Jan 28, 2014

In developed countries, the majority of all violent crime is committed by a small group of antiso... more In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal viole...

American journal of psychotherapy, 2011

The perceptions of patients (n = 25) and their therapists about psychodynamic psychotherapy for d... more The perceptions of patients (n = 25) and their therapists about psychodynamic psychotherapy for depression were assessed during the first treatment year using 23 scales. Patients and therapists independently evaluated the impact of depression on the therapeutic experience of the patients. The estimations of the impact of depression by the patients and therapists were concordant in the majority of the subjects, reflecting mutual tuning and a working alliance. The roles of affects and frustrating subjects in the treatment relationship were evaluated as significantly different by the patients and the therapists. The results highlight the importance of working on the expression of affects in the psychotherapy of depression.