Prenatal exposure to maternal cigarette smoking and structural properties of the human corpus callosum.

Alterations induced by prenatal exposure to nicotine have been observed in experimental (rodent) studies. While numerous developmental outcomes have been associated with prenatal exposure to maternal cigarette smoking (PEMCS) in humans, the possible relation with brain structure is less clear. Here we sought to elucidate the relation between PEMCS and structural properties of human corpus callosum in adolescence and early adulthood in a total of 1,747 youth. We deployed three community-based cohorts of 446 (age 25-27 years, 46% exposed), 934 (age 12-18 years, 47% exposed) and 367 individuals (age 18-21 years, 9% exposed). A mega-analysis revealed lower mean diffusivity in the callosal segments of exposed males. We speculate that prenatal exposure to maternal cigarette smoking disrupts the early programming of callosal structure and increases the relative portion of small-diameter fibres.

Mortality by diseases and medical conditions in the offspring of parents with severe mental illness.

PURPOSE: The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. There might be common familial pathway leading to a high co-occurrence of somatic disorders and SMI. To study this we explored the long-term mortality for natural causes in the offspring of people with SMI. METHODS: Participants were members of the Northern Finland Birth Cohort 1966 (NFBC1966; N = 11,325). The data on cause of deaths of the members were obtained from the Population Register Center until year 2015. The data on hospital-treated psychiatric disorders of parents were obtained from nationwide Care Register for Health Care. Cumulative incidences by age were calculated in the NFBC1966 members having a parent with SMI and those who did not have. We were able to take into account multiple confounders. RESULTS: Of the total sample of 11,325 offspring, 853 (7.4%) died during the follow-up period, 74 (8.7%) from the study cohort and 779 (91.3%) from the comparison group. These numbers included 160 stillborn children. There were 557 cases of deaths from diseases and medical conditions and 296 deaths from external causes. The adjusted risk ratio for offspring of mothers with SMI was 1.08 (0.72-1.64), and for offspring of fathers with SMI 0.58 (0.36-0.93). CONCLUSIONS: This was the first long-term follow-up study (up to age 49) of all-cause mortality in offspring of parents with SMI. Our findings were contrary to expectations. Offspring of parents with SMI had no increased risk for dying. In fact, the risk for dying in the group of offspring of fathers with SMI was lower than in the comparison group. This study does not support the assumption of common familial pathway leading to a high co-occurrence of somatic disorders and SMI.

The Finnish psychiatric birth cohort consortium (PSYCOHORTS) - content, plans and perspectives.

Background: Psychiatric disorders tend to be developmental, and longitudinal settings are required to examine predictors of psychiatric phenomena. Replicating and combining data and results from different birth cohorts, which are a source of reliable data, can make research even more valuable. The Finnish Psychiatric Birth Cohort Consortium (PSYCOHORTS) project combines birth cohorts in Finland. Aim: The aim of this paper is to introduce content, plans and perspectives of the PSYCOHORTS project that brings together researchers from Finland. In addition, we illustrate an example of data harmonization using available data on causes of death. Content: PSYCOHORTS includes eight Finnish birth cohorts. The project has several plans: to harmonize different data from birth cohorts, to incorporate biobanks into psychiatric birth cohort research, to apply multigenerational perspectives, to integrate longitudinal patterns of marginalization and inequality in mental health, and to utilize data in health economics research. Data on causes of death, originally obtained from Finnish Cause of Death register, were harmonized across the six birth cohorts using SAS macro facility. Results: Harmonization of the cause of death data resulted in a total of 21,993 observations from 1965 to 2015. For example, the percentage of deaths due to suicide and the sequelae of intentional self-harm was 14% and alcohol-related diseases, including accidental poisoning by alcohol, was 13%. Conclusions: PSYCOHORTS lays the foundation for complex examinations of psychiatric disorders that is based on compatible datasets, use of biobanks and multigenerational approach to risk factors, and extensive data on marginalization and inequality.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Longitudinal associations between childhood and adulthood externalizing and internalizing psychopathology and adolescent substance use.

BACKGROUND: Emotional and behavioral problems are commonly associated with substance use in adolescence but it is unclear whether substance use precedes or follows mental health problems. The aim was to investigate longitudinal associations between externalizing and internalizing psychopathology and substance use in a prospective population study design. METHOD: The sample was the Northern Finland Birth Cohort 1986 Study (NFBC 1986; n = 6349; 3103 males). Externalizing and internalizing mental health problems were assessed at age 8 years (Rutter scales), substance use and externalizing and internalizing problems [Youth Self-Report (YSR)] at age 15-16 years, and hospital diagnoses for internalizing disorders (age 25) and criminal offences (age 20) from nationwide registers in adulthood. RESULTS: Externalizing problems at age 8 were associated with later substance use. After adjustment for sociodemographic factors, parental alcohol use and psychiatric disorders, and earlier externalizing and internalizing problems, substance use predicted criminality, especially among males, with the highest odds ratio (OR) for cannabis use [adjusted OR 6.2, 95% confidence interval (CI) 3.1-12.7]. Early internalizing problems were not a risk for later substance use. Female adolescent cannabis (OR 3.2, 95% CI 1.4-7.3) and alcohol (OR 2.1, 95% CI 1.1-4.2) use predicted internalizing disorders in adulthood. CONCLUSIONS: Externalizing problems precede adolescent substance use in both genders, whereas, among boys, substance use also precedes criminal offences. Internalizing problems may follow substance use in females. These associations were robust even when taking into account previous mental health problems.

Response initiation in young adults at risk for psychosis in the Northern Finland 1986 Birth Cohort.

INTRODUCTION: This is one of the very few studies to investigate the specific executive function/processing speed component of response initiation in subjects at familial risk (FR) for psychosis, and the first such study in subjects at clinical risk (CR) for psychosis. METHODS: Participants (N = 177) were members of the general population-based Northern Finland 1986 Birth Cohort in the following four groups: FR for psychosis (n = 62), CR for psychosis (n = 21), psychosis (n = 25) and control subjects (n = 69). The response initiation of these groups was compared in three different tests: Semantic fluency, Stockings of Cambridge and Spatial working memory. RESULTS: The two risk groups did not differ significantly from control group, but differed from, and outperformed the psychosis group in semantic fluency response initiation. CONCLUSIONS: Response initiation deficits were not evident in a non-help seeking psychosis high-risk sample.

Association of obesity to reaction time and visual memory in schizophrenia.

Background: Both overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders. Aims: Our aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder. Methods: The study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory. Results: Obesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures. Conclusions: The results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.

Insulin resistance and lipid levels in adolescents with familial risk for psychosis.

OBJECTIVE: Type 2 diabetes and dyslipidemias co-occur frequently with schizophrenia. It is not known how common they are in adolescents with a familial risk for psychosis. METHOD: The Northern Finland 1986 Birth Cohort consists of 9432 children born alive in the two Northernmost provinces in Finland. At the age of 15/16 they participated in clinical examination including measurements of glucose, lipids and IR, and a questionnaire including items about their diet and physical activity. The Finnish Hospital Discharge Register was used to find out non-organic psychoses in parents during 1972-2000. This familial risk was found out in 54 boys and 68 girls. Their results were compared with other cohort members. RESULTS: No differences were observed in the cardiometabolic risk factors between the study groups. CONCLUSION: Our results suggest that familial risk for psychosis is not directly associated with disturbances of glucose and lipid metabolism among adolescents.

Childhood family structure and personality disorders in adulthood.

BACKGROUND: The association between childhood family structure and sociodemographic characteristics and personality disorders (PDs) in a general population sample was studied. METHODS: This study is a substudy of the prospective Northern Finland 1966 Birth Cohort Project with 1588 young adult subjects. The case-finding methods according to the DSM-III-R criteria for PDs were: (1) Structured Clinical Interview for DSM-III-R (SCID) for 321 cases who participated in a 2-phase field study, (2) Finnish Hospital Discharge Register data, and (3) analysis of the patient records in public outpatient care in 1982-1997. Statistical analyses were performed on the association between PDs and family background factors. RESULTS: Altogether 110 (7.0%) of the subjects had at least one probable or definite PD. After adjusting for confounders (gender, parental social class and parental psychiatric disorder) the results indicated that single-parent family type in childhood was associated with cluster B PDs in adulthood. Being an only child in childhood was associated with cluster A PDs. No special childhood risk factors were found for cluster C PDs. CONCLUSIONS: Results suggest that single-parent family type at birth and being an only child in the 1960s are associated with PD in adulthood. Further studies are needed to explore the psychosocial aspects of family environment which may nowadays promote vulnerability to PDs in adulthood.

Outcome and its predictors in schizophrenia within the Northern Finland 1966 Birth Cohort.

PURPOSE: We report clinical and social outcomes of schizophrenia in the longitudinal, population-based Northern Finland 1966 Birth Cohort, and describe associated demographic, developmental and illness-related factors. SUBJECTS AND METHODS: Subjects with DSM-III-R schizophrenia (n=59) were followed prospectively from mid-gestation up to age 35 years. Outcome measures included positive and negative symptoms, psychiatric hospitalisations, social and occupational functioning. Several definitions of good and poor outcome were explored, and developmental, socio-demographic and clinical predictors of outcomes were analysed. RESULTS: Good clinical outcome varied from 10% to 59%, and good social outcome 15-46%, depending on definition. Poor clinical outcome varied 41-77% and poor social 37-54%. Lack of friends in childhood, father's high social class, lower school performance and earlier age of illness onset predicted poor outcomes. DISCUSSION: The outcomes of schizophrenia in this study depended on definitions used but were relatively poor. The age of illness onset, father's social class, school performance and poor social contacts in childhood were only statistically significant predictors. CONCLUSION: Definitions of outcome have a major effect on estimates for proportions of good and bad outcomes and on the predictors of outcomes. However, regardless of which definitions were used, the outcome of schizophrenia in this population-based sample was generally bleak.

A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Infant motor development and adult cognitive functions in schizophrenia.

BACKGROUND: Childhood neuromotor dysfunction is a risk factor for schizophrenia, a disorder in which cognitive deficits are prominent. The relationship between early neurodevelopment and adult cognition in schizophrenia remains unclear. METHODS: We examined the associations between infant motor development and adult cognitive functions in schizophrenia (n = 61) and the general population (n = 104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on ages of learning to stand and walk with or without support were obtained at age 12 months by health visitor assessment. Neurocognitive measures at age 33-35 included executive function, verbal and visual episodic memory, and visuo-spatial working memory. RESULTS: The schizophrenia group achieved neuromotor milestones later and performed significantly worse than the control group on all measures of cognition. In pooled analyses there were associations between infant motor development and adult cognition in the domains of executive function, verbal learning and visuospatial working memory, but not in visual object learning. The pattern of associations between development and cognition was similar in schizophrenia and the general population. CONCLUSIONS: These findings are consistent with the hypothesis that in schizophrenia mild infant motor developmental delay and adult cognitive deficits (at least in some domains) are age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome.

Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966.

BACKGROUND: Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes. METHODS: The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers. RESULTS: During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score. CONCLUSIONS: In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.

Brain structural changes in women and men during midlife.

Brain development during childhood and adolescence differs between boys and girls. Structural changes continue during adulthood and old age, particularly in terms of brain volume reductions that accelerate beyond age 35 years. We investigated whether brain structural change in mid-life differs between men and women. 43 men and 28 women from the Northern Finland 1966 Birth Cohort underwent MRI brain scans at age 33-35 (SD=0.67) and then again at age 42-44 (SD=0.41). We examined sex differences in total percentage brain volume change (PBVC) and regional brain change with FSL SIENA software. Women showed significant PBVC reduction compared with men between the ages of 33-35 and 42-44 years (Mean=-3.21% in men, Mean=-4.03% in women, F (1, 68)=6.37, p<0.05). In regional analyses, women exhibited greater brain reduction than men in widespread areas. After controlling for total percent brain volume change, men show greater relative regional brain reduction than women in bilateral precentral gyri, bilateral paracingulate gyri, and bilateral supplementary motor cortices. The results indicate sex differences in brain changes in mid-life. Women have more total brain reduction, and more reduction on the outer brain surface than men, whereas men exhibit more brain reduction on the mid-line surface than women after co-varying for total brain volume loss. These changes could contribute to sex differences in midlife behaviour and health.

Brain morphometry of individuals with schizophrenia with and without antipsychotic medication ­ The Northern Finland Birth Cohort 1966 Study.

BACKGROUND: In schizophrenia, brain morphometric changes may be associated with antipsychotic medication. Only limited data is available concerning individuals with schizophrenia without antipsychotic medication. We aimed to study the associations of: use versus no use of antipsychotic medication; length of continuous time without antipsychotic medication; cumulative dose of lifetime antipsychotic medication; and type of antipsychotic medication; with brain morphometry in schizophrenia after an average of 10 years of illness. METHODS: Data of 63 individuals with schizophrenia (mean duration of illness 10.4 years) from the Northern Finland Birth Cohort 1966 were gathered by interview and from hospital and outpatient records. Structural MRI data at age 34 years were acquired and grey matter volume maps with voxel-based morphometry were analyzed using FSL tools. RESULTS: Of the individuals studied, 15 (24%) had taken no antipsychotic medication during the previous year. Individuals with antipsychotic medication had lower total grey matter (TGM) volume compared with non-medicated subjects, although this association was not statistically significant (Cohen's d=-0.51, P=0.078). Time without antipsychotic medication associated with increased TGM (P=0.028). Longer time without antipsychotic medication associated with increased regional volume in right precentral gyrus and right middle frontal gyrus. There were no associations between cumulative dose of lifetime antipsychotic medication or type of antipsychotic medication and brain morphometry. CONCLUSIONS: Unlike some previous investigators, we found no association between cumulative dose of lifetime antipsychotic medication and brain morphological changes in this population-based sample. However, longer continuous time without antipsychotic medication preceding the MRI scan associated with increased gray matter volume.

Neurocognition as a predictor of outcome in schizophrenia in the Northern Finland Birth Cohort 1966.

The purpose of this study was to study neurocognitive performance as a predictor of outcomes in midlife schizophrenia. There is a lack of studies with unselected samples and a long follow-up. The study is based on the prospective, unselected population-based Northern Finland Birth Cohort 1966. The study includes 43 individuals with schizophrenia and 73 controls, whose neurocognitive performance was assessed twice, at 34 and 43 years. At both time points we used identical neurocognitive tests to assess verbal and visual memory and executive functions. Our main aim was to analyse neurocognitive performance at 34 years as a predictor of clinical, vocational and global outcomes at 43 years. Additionally, the analysis addressed cross-sectional associations between cognitive performance and clinical, vocational and global measures at 43 years. The assessment of outcomes was performed in the schizophrenia group only. In the longitudinal analysis poorer visual memory predicted poorer vocational outcome and poorer long-term verbal memory predicted poorer global outcome. In the cross-sectional analysis poorer visual memory and lower composite score of neurocognition were associated with poorer global outcome. No individual neurocognitive test or the composite score of these predicted remission. These data indicate that neurocognition, especially memory function, is an important determinant of long-term functional outcome in midlife schizophrenia.

Early developmental milestones in adult schizophrenia and other psychoses. A 31-year follow-up of the Northern Finland 1966 Birth Cohort.

Delayed childhood development may precede adult psychoses. We tested this hypothesis in a large, general population birth cohort (n=12058) followed to age 31 years. The ages at which individuals learned to stand, walk, speak, and became potty-trained (bowel control) and dry (bladder control), were recorded at a 1-year examination. Psychiatric outcome was ascertained through linkage to a national hospital discharge register. Cumulative incidence of DSM-III-R schizophrenia, other psychoses and non-psychotic disorders were stratified according to the timing of milestones and compared within the cohort using internal standardization. 100 cases of DSM-III-R schizophrenia, 55 other psychoses, and 315 non-psychotic disorders were identified. The ages at learning to stand, walk and become potty-trained were each related to subsequent incidence of schizophrenia and other psychoses. Compared with the whole cohort, earlier milestones reduced, and later milestones increased, the risk in a linear manner. These developmental effects were not seen for non-psychotic outcomes. The findings support hypotheses regarding psychosis as having a developmental dimension with precursors apparent in early life.

Digital imaging and microtexture analysis of the nerve fiber layer.

PURPOSE: To describe the design of a digital retinal nerve fiber layer (RNFL) imaging techniques and present a new approach to measure the differences in RNFL patterns. METHODS: A digital camera body is connected to a wide-angle camera to obtain images of the RNFL, which are displayed in workstations throughout the clinic. In the on-line archive, images in Joint Photographics Experts Group (JPEG) format (100 KB per frame) are used. The hypothesis that changes in RNFL structure can be seen as changes in the microtexture of digital images was tested using an information theoretical approach (Kullback Information Distance, KID). A large KID value indicates a large difference, and a small KID value indicates a small difference in microtexture between the two regions. The material of this pilot study consists of 9 patients with glaucoma, 8 patients with ocular hypertension, and 7 normal subjects. RESULTS: The median KID value in the glaucoma group was 3.5, compared with the median KID values of 0.6 in the control groups. Although a trend could be seen in the measured values, because of a small sample size, the differences were not statistically significant. Five of 24 (21%) KID values overlapped between the glaucomatous group and the other two groups. CONCLUSION: Although digital imaging produces good quality RNFL images, further research is needed to establish minimum accepted specifications for digital imaging. In this pilot study, only the microtexture of the RNFL was measured in digital images. In the future, the approach can be expanded to include also properties of macrotexture and full color palette.

Psychiatric disorders and their predictors in young adulthood in Finland.

Mental disorders are one main focus of research interest in the 31 year study of the Northern Finland 1966 Birth Cohort Study. Mental disorders are quite common in young adulthood and they have a great impact on quality of life and working ability. Good national registers in Finland ensure the possibility to follow up treated incidence of severe mental disorders. On the other hand, a notable part of those who suffer from non-psychotic mental disorders do not receive any psychiatric treatment. That is why it is not possible to follow up psychiatric morbidity of the non-psychotic disorders from register data. In this review, principles of psychiatric diagnostics, known prevalences of psychiatric disorders in population and factors connected with mental disorder are briefly presented. Especially childhood predictors of mental disorders are reviewed.

Association between symptoms of temporomandibular disorders and depression: an epidemiological study of the Northern Finland 1966 Birth Cohort.

Facial pain and other symptoms of temporomandibular disorders (TMD) are rather common in the adult population. According to clinical studies, psychological factors play an important role in the etiology and maintenance of these symptoms. On the other hand, chronic pain can cause depression. The aim of this study was to evaluate the association between symptoms of TMD and depression in a large population sample of young adults. The study was a part of the 31-year follow-up study of the Northern Finland Birth Cohort consisting of 12,058 live births from the year 1966. Questionnaire information concerning TMD symptoms was collected from a subsample of 5,696 subjects. Depression was measured with a question about reported depression (diagnosed by a doctor) and with the Symptom Checklist depression subscale (SCL-25 DS). Of the TMD symptoms, those related to pain had the most significant relations to indicators of depression. In both genders, the proportion of depression indicated with the SCL-25 DS was significantly higher in subjects with pain-related symptoms of TMD, i.e., facial pain and "pain at jaw rest", and in men with "pain on jaw movement", compared with non-pain subjects (p<0.05). Other symptoms of TMD also associated significantly with SCL-25 DS (p>0.05), except "difficulties in mouth opening" among women. Among women, the prevalence of recognized depression was also significantly higher in subjects with pain-related symptoms of TMD, compared with subjects with no pain (p< or =0.05). Almost all the associations remained significant after adjusting for marital status, education, and self-rated general health. In conclusion, the results show that depression has an association with TMD symptoms, especially those related to pain. When treating patients with facial pain, dentists should consider the possible presence of psychopathology and, if necessary, consult appropriate mental health professionals.