Implications of co-twin dependence for twins' social interactions, mental health and alcohol use : A follow-up study of Finnish twins from adolescence to early adulthood

Objective: The aim of the present study was to examine co-twin dependence and its impact on twins' social contacts, leisure-time activities and psycho-emotional well-being. The role of co-twin dependence was also examined as a moderator of genetic and environmental influences on alcohol use in adolescence and in early adulthood. Methods: The present report is based on the Finnish Twin Cohort Study (FinnTwin16), a population-based study of five consecutive birth cohorts of Finnish twins born in the years 1975-1979. Baseline assessments were collected through mailed questionnaires, within two months of the twins' sixteenth birthday yielding replies from 5563 twin individuals. All respondent twins were sent follow-up questionnaires at ages of 17, 18½, and in early adulthood, when twins were 22-27 years old. Measures: The questionnaires included a survey of health habits and attitudes, a symptom checklist and questions about twins' relationships with parents, peers and co-twin. Measures used were twins' self-reports of their own dependence and their co-twin's dependence at age 16, reports of twins' leisure-time activities and social contacts, alcohol use, psychological distress and somatic symptoms both in adolescence and in early adulthood. Results: In the present study 25.6% of twins reported dependence on their co-twin. There were gender and zygosity differences in dependence, females and MZ twins were more likely to report dependence than males and DZ twins. Co-twin dependence can be viewed on one hand as an individual characteristic, but on the other hand as a pattern of dyadic interaction that is mutually regulated and reciprocal. Most of the twins (80.7%) were either concordantly co-twin dependent or concordantly co-twin independent. The associations of co-twin dependence with twins' social interactions and psycho-emotional characteristics were relatively consistent both in adolescence and in early adulthood. Dependence was related to higher contact frequency and a higher proportion of shared leisure-time activities between twin siblings at the baseline and the follow-up. Additionally co-twin dependence was associated with elevated levels of psycho-emotional distress and somatic complaints, especially in adolescence. In the framework of gene-environment interaction, these results suggest that the genetic contribution to individual differences in drinking patterns is dependent on the nature of the pair-wise relationship of twin siblings. Conclusions: The results of this study indicate that co-twin dependence is a genuine feature of the co-twin relationship and shows the importance of studying the impact of various features of co-twin relationships on individual twins' social and psycho-emotional life and well-being. Our study also offers evidence that differences in inter-personal relationships contribute to the effects of genetic propensities.

Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has a relatively high heritability, and on the other hand adenosine regulates sleep homeostasis and might also be involved in mood modulation, adenosine-related genes should be considered for their possible contribution to a predisposition for depression and disturbed sleep in humans. Depression is a complex disorder likely involving the abnormal functioning of several genes. Novel target genes which could serve as the possible common substrates for depression and comorbid disturbed sleep should be identified. In this way specific brain areas related to sleep regulation should be studied by using animal model of depression which represents more homogenous phenotype as compared to humans. It is also important to study these brain areas during the development of depressive-like features to understand how early changes could facilitate pathophysiological changes in depression. Aims and methods: We aimed to find out whether, in the basal forebrain, adenosine induces recovery non-rapid eye movement (NREM) sleep after prolonged waking through the A1 or/and A2A receptor subtype. A1 and A2A receptor antagonists were perfused into the rat basal forebrain during 3 h of sleep deprivation, and the amount of NREM sleep and delta power during recovery NREM sleep were analyzed. We then explored whether polymorphisms in genes related to the metabolism, transport and signaling of adenosine could predispose to depression accompanied by signs of disturbed sleep. DNA from 1423 individuals representative of the Finnish population and including controls and cases with depression, depression accompanied by early morning awakenings and depression accompanied by fatigue, was used in the study to investigate the possible association between polymorphisms from adenosine-related genes and cases. Finally to find common molecular substrates of depression and disturbed sleep, gene expression changes were investigated in specific brain areas in the rat clomipramine model of depression. We focused on the basal forebrain of 3-week old clomipramine-treated rats which develop depressive-like symptoms later in adulthood and on the hypothalamus of adult female clomipramine-treated rats. Results: Blocking of the A1 receptor during sleep deprivation resulted in a reduction of the recovery NREM sleep amount and delta power, whereas A2A receptor antagonism had no effect. Polymorphisms in adenosine-related genes SLC29A3 (equilibrative nucleoside transporter type 3) in women and SLC28A1 (concentrative nucleoside transporter type 1) in men associated with depression alone as well as when accompanied by early morning awakenings and fatigue. In Study III the basal forebrain of postnatal rats treated with clomipramine displayed disturbances in gamma-aminobutyric acid (GABA) receptor type A signaling, in synaptic transmission and possible epigenetic changes. CREB1 was identified as a common transcription denominator which also mediates epigenetic regulation. In the hypothalamus the major changes included the expression of genes in GABA-A receptor pathway, K+ channel-related, glutamatergic and mitochondrial genes, as well as an overexpression of genes related to RNA and mRNA processing. Conclusions: Adenosine plays an important role in sleep homeostasis by promoting recovery NREM sleep via the A1 receptor subtype in the basal forebrain. Also adenosine levels might contribute to the risk of depression with disturbed sleep, since the genes encoding nucleoside transporters showed the strongest associations with depression alone and when accompanied by signs of disturbed sleep in both women and men. Sleep and mood abnormalities in major depressive disorder could be a consequence of multiple changes at the transcriptional level, GABA-A receptor signaling and synaptic transmission in sleep-related basal forebrain and the hypothalamus.

Functional and work disability and treatment received by patients with major depressive disorder

This study is one part of a collaborative depression research project, the Vantaa Depression Study (VDS), involving the Department of Mental and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry of the Peijas Medical Care District (PMCD), Vantaa, Finland. The VDS includes two parts, a record-based study consisting of 803 patients, and a prospective, naturalistic cohort study of 269 patients. Both studies include secondary-level care psychiatric out- and inpatients with a new episode of major depressive disorder (MDD). Data for the record-based part of the study came from a computerised patient database incorporating all outpatient visits as well as treatment periods at the inpatient unit. We included all patients aged 20 to 59 years old who had been assigned a clinical diagnosis of depressive episode or recurrent depressive disorder according to the International Classification of Diseases, 10th edition (ICD-10) criteria and who had at least one outpatient visit or day as an inpatient in the PMCD during the study period January 1, 1996, to December 31, 1996. All those with an earlier diagnosis of schizophrenia, other non-affective psychosis, or bipolar disorder were excluded. Patients treated in the somatic departments of Peijas Hospital and those who had consulted but not received treatment from the psychiatric consultation services were excluded. The study sample comprised 290 male and 513 female patients. All their psychiatric records were reviewed and each patient completed a structured form with 57 items. The treatment provided was reviewed up to the end of the depression episode or to the end of 1997. Most (84%) of the patients received antidepressants, including a minority (11%) on treatment with clearly subtherapeutic low doses. During the treatment period the depressed patients investigated averaged only a few visits to psychiatrists (median two visits), but more to other health professionals (median seven). One-fifth of both genders were inpatients, with a mean of nearly two inpatient treatment periods during the overall treatment period investigated. The median length of a hospital stay was 2 weeks. Use of antidepressants was quite conservative: The first antidepressant had been switched to another compound in only about one-fifth (22%) of patients, and only two patients had received up to five antidepressant trials. Only 7% of those prescribed any antidepressant received two antidepressants simultaneously. None of the patients was prescribed any other augmentation medication. Refusing antidepressant treatment was the most common explanation for receiving no antidepressants. During the treatment period, 19% of those not already receiving a disability pension were granted one due to psychiatric illness. These patients were nearly nine years older than those not pensioned. They were also more severely ill, made significantly more visits to professionals and received significantly more concomitant medications (hypnotics, anxiolytics, and neuroleptics) than did those receiving no pension. In the prospective part of the VDS, 806 adult patients were screened (aged 20-59 years) in the PMCD for a possible new episode of DSM-IV MDD. Of these, 542 patients were interviewed face-to-face with the WHO Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Version 2.0. Exclusion criteria were the same as in the record-based part of the VDS. Of these, 542 269 patients fulfiled the criteria of DSM-IV MDE. This study investigated factors associated with patients' functional disability, social adjustment, and work disability (being on sick-leave or being granted a disability pension). In the beginning of the treatment the most important single factor associated with overall social and functional disability was found to be severity of depression, but older age and personality disorders also significantly contributed. Total duration and severity of depression, phobic disorders, alcoholism, and personality disorders all independently contributed to poor social adjustment. Of those who were employed, almost half (43%) were on sick-leave. Besides severity and number of episodes of depression, female gender and age over 50 years strongly and independently predicted being on sick-leave. Factors influencing social and occupational disability and social adjustment among patients with MDD were studied prospectively during an 18-month follow-up period. Patients' functional disability and social adjustment were alleviated during the follow-up concurrently with recovery from depression. The current level of functioning and social adjustment of a patient with depression was predicted by severity of depression, recurrence before baseline and during follow-up, lack of full remission, and time spent depressed. Comorbid psychiatric disorders, personality traits (neuroticism), and perceived social support also had a significant influence. During the 18-month follow-up period, of the 269, 13 (5%) patients switched to bipolar disorder, and 58 (20%) dropped out. Of the 198, 186 (94%) patients were at baseline not pensioned, and they were investigated. Of them, 21 were granted a disability pension during the follow-up. Those who received a pension were significantly older, more seldom had vocational education, and were more often on sick-leave than those not pensioned, but did not differ with regard to any other sociodemographic or clinical factors. Patients with MDD received mostly adequate antidepressant treatment, but problems existed in treatment intensity and monitoring. It is challenging to find those at greatest risk for disability and to provide them adequate and efficacious treatment. This includes great challenges to the whole society to provide sufficient resources.

Genotype-Phenotype Relationships in Long QT Syndrome: Role of Mental Stress, Adrenergic Activity and a Common KCNH2 Polymorphism

Long QT syndrome is a congenital or acquired arrhythmic disorder which manifests as a prolonged QT-interval on the electrocardiogram and as a tendency to develop ventricular arrhythmias which can lead to sudden death. Arrhythmias often occur during intense exercise and/or emotional stress. The two most common subtypes of LQTS are LQT1, caused by mutations in the KCNQ1 gene and LQT2, caused by mutations in the KCNH2 gene. LQT1 and LQT2 patients exhibit arrhythmias in different types of situations: in LQT1 the trigger is usually vigorous exercise whereas in LQT2 arrhythmia results from the patient being startled from rest. It is not clear why trigger factors and clinical outcome differ from each other in the different LQTS subtypes. It is possible that stress hormones such as catecholamines may show different effects depending on the exact nature of the genetic defect, or sensitivity to catecholamines varies from subject to subject. Furthermore, it is possible that subtle genetic variants of putative modifier genes, including those coding for ion channels and hormone receptors, play a role as determinants of individual sensitivity to life-threatening arrhythmias. The present study was designed to identify some of these risk modifiers. It was found that LQT1 and LQT2 patients show an abnormal QT-adaptation to both mental and physical stress. Furthermore, as studied with epinephrine infusion experiments while the heart was paced and action potentials were measured from the right ventricular septum, LQT1 patients showed repolarization abnormalities which were related to their propensity to develop arrhythmia during intense, prolonged sympathetic tone, such as exercise. In LQT2 patients, this repolarization abnormality was noted already at rest corresponding to their arrhythmic episodes as a result of intense, sudden surges in adrenergic tone, such as fright or rage. A common KCNH2 polymorphism was found to affect KCNH2 channel function as demonstrated by in vitro experiments utilizing mammalian cells transfected with the KCNH2 potassium channel as well as QT-dynamics in vivo. Finally, the present study identified a common β-1-adrenergic receptor genotype that is related a shorter QT-interval in LQT1 patients. Also, it was discovered that compound homozygosity for two common β-adrenergic polymorphisms was related to the occurrence of symptoms in the LQT1 type of long QT syndrome. The studies demonstrate important genotype-phenotype differences between different LQTS subtypes and suggest that common modifier gene polymorphisms may affect cardiac repolarization in LQTS. It will be important in the future to prospectively study whether variant gene polymorphisms will assist in clinical risk profiling of LQTS patients.

Long-term Outcome of DSM-IV Major Depressive Disorder in Psychiatric Care

Much of what we know regarding the long-term course and outcome of major depressive disorder (MDD) is based on studies of mostly inpatient tertiary level cohorts and samples predating the era of the current antidepressants and the use of maintenance therapies. In addition, there is a lack of studies investigating the comprehensive significance of comorbid axis I and II disorders on the outcome of MDD. The present study forms a part of the Vantaa Depression Study (VDS), a regionally representative prospective and naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients (aged 20-59) with a new episode of DSM-IV MDD, and followed-up up to five years (n=182) with a life-chart and semistructured interviews. The aim was to investigate the long-term outcome of MDD and risk factors for poor recovery, recurrences, suicidal attempts and diagnostic switch to bipolar disorder, and the association of a family history of different psychiatric disorders on the outcome. The effects of comorbid disorders together with various other predictors from different domains on the outcome were comprehensively investigated. According to this study, the long-term outcome of MDD appears to be more variable when its outcome is investigated among modern, community-treated, secondary-care outpatients compared to previous mostly inpatient studies. MDD was also highly recurrent in these settings, but the recurrent episodes seemed shorter, and the outcome was unlikely to be uniformly chronic. Higher severity of MDD predicted significantly the number of recurrences and longer time spent ill. In addition, longer episode duration, comorbid dysthymic disorder, cluster C personality disorders and social phobia predicted a worse outcome. The incidence rate of suicide attempts varied robustly de¬pending on the level of depression, being 21-fold during major depressive episodes (MDEs), and 4-fold during partial remission compared to periods of full remission. Although a history of previous attempts and poor social support also indicated risk, time spent depressed was the central factor determining overall long-term risk. Switch to bipolar disorder occurred mainly to type II, earlier to type I, and more gradually over time to type II. Higher severity of MDD, comorbid social phobia, obsessive compulsive disorder, and cluster B personality disorder features predicted the diagnostic switch. The majority of patients were also likely to have positive family histories not exclusively of mood, but also of other mental disorders. Having a positive family history of severe mental disorders was likely to be clinically associated with a significantly more adverse outcome.

Recognition, comorbidity, and outcome of DSM-IV bipolar I and II disorders in psychiatric care

This study is part of an ongoing collaborative bipolar research project, the Jorvi Bipolar Study (JoBS). The JoBS is run by the Department of Mental Health and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital (HUCH), Espoo, Finland. It is a prospective, naturalistic cohort study of secondary level care psychiatric in- and outpatients with a new episode of bipolar disorder (BD). The second report also included 269 major depressive disorder (MDD) patients from the Vantaa Depression Study (VDS). The VDS was carried out in collaboration with the Department of Psychiatry of the Peijas Medical Care District. Using the Mood Disorder Questionnaire (MDQ), all in- and outpatients at the Department of Psychiatry at Jorvi Hospital who currently had a possible new phase of DSM-IV BD were sought. Altogether, 1630 psychiatric patients were screened, and 490 were interviewed using a semistructured interview (SCID-I/P). The patients included in the cohort (n=191) had at intake a current phase of BD. The patients were evaluated at intake and at 6- and 18-month interviews. Based on this study, BD is poorly recognized even in psychiatric settings. Of the BD patients with acute worsening of illness, 39% had never been correctly diagnosed. The classic presentations of BD with hospitalizations, manic episodes, and psychotic symptoms lead clinicians to correct diagnosis of BD I in psychiatric care. Time of follow-up elapsed in psychiatric care, but none of the clinical features, seemed to explain correct diagnosis of BD II, suggesting reliance on cross- sectional presentation of illness. Even though BD II was clearly less often correctly diagnosed than BD I, few other differences between the two types of BD were detected. BD I and II patients appeared to differ little in terms of clinical picture or comorbidity, and the prevalence of psychiatric comorbidity was strongly related to the current illness phase in both types. At the same time, the difference in outcome was clear. BD II patients spent about 40% more time depressed than BD I patients. Patterns of psychiatric comorbidity of BD and MDD differed somewhat qualitatively. Overall, MDD patients were likely to have more anxiety disorders and cluster A personality disorders, and bipolar patients to have more cluster B personality disorders. The adverse consequences of missing or delayed diagnosis are potentially serious. Thus, these findings strongly support the value of screening for BD in psychiatric settings, especially among the major depressive patients. Nevertheless, the diagnosis must be based on a clinical interview and follow-up of mood. Comorbidity, present in 59% of bipolar patients in a current phase, needs concomitant evaluation, follow-up, and treatment. To improve outcome in BD, treatment of bipolar depression is a major challenge for clinicians.

Suicidal behaviour in bipolar disorder

The Jorvi Bipolar Study (JoBS) is a collaborative ongoing bipolar research project between the Department of Mental Health and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital (HUCH), Espoo, Finland. The JoBS is a prospective, naturalistic cohort study of secondary level care psychiatric out-and inpatients with a new episode of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) bipolar disorder (BD). Altogether, 1630 patients (aged 18-59) years were screened using the Mood Disorder Questionnaire (MDQ) for a possible new episode of DSM-IV BD. 490 patients were interviewed with semi-structured interview [the Structured Clinical Interview for DSM-IV Disorders, research version with Psychotic Screen (SCID-I/P)]. 191 patients with new episode of DSM-IV BD were included in the bipolar cohort study. Psychiatric comorbidity was evaluated using semi-structured interviews. At 6- and 18-month follow-up, the interviews were repeated and life-chart methodology was used to integrate all available information about nature and duration of all different phases. Suicidal behaviour was examined both at intake and follow-up by psychometric scale [Scale for Suicidal Ideation (SSI)], interviewer s questions and medical and psychiatric records. The aim of this thesis was to evaluate prevalence of suicidal behaviour and incidence of suicide attempts, and examine the wide range of risk factors for attempted suicide both, at intake and follow-up, in representative secondary-level sample of psychiatric in- and outpatients with BD. In this study suicidal behaviour was common among psychiatric patients with BD. During the episode when patients were included into cohort study (index episode), 20% of the patients had attempted suicide and 61% had suicidal ideation. Severity of depressive episode and hopelessness were independent risk factors for suicidal ideation, whereas hopelessness, comorbid personality disorder and previous suicide attempt predicted suicide attempts during the index episode. There were no differences in prevalence of suicidal behaviour between bipolar I and II disorder; the risk factors were overlapping but not identical. During the index episode, suicide attempts took place during depressive, mixed and depressive mixed phases. Furthermore, there were marked differences regarding level of suicidal ideation during different phases, with the highest levels during the mixed phases of the illness. Hopelessness was independently associated with suicidal behaviour during the depressive phase. A subjective rating of severity of depression (Beck Depression Inventory) and younger age predicted suicide attempts during mixed phases. During the 18-month follow-up 20% of patients attempted suicide. Previous suicide attempts, hopelessness, depressive phase at index episode and younger age at intake were independent risk factors for suicide attempts during follow-up. Taken altogether, 55% patients attempted suicide before index episode, during index episode or during follow-up. The incidence of suicide attempts was 37-fold during combined mixed and depressive mixed states and 18-fold during major depressive phase as compared with other phases. Prior suicide attempt and time spent in combined mixed phases - mixed and depressive mixed - and depressive phases independently predicted the suicide attempt during follow-up. More than half of the patients have attempted suicide during their lifetime, a finding which highlights the public health importance of suicidal behaviour in bipolar disorder. Clinically, it is crucial to recognize BD and manage the mixed and depressive phases of bipolar patients fast and effectively, as time spent in depressive and mixed phases involves a remarkably high risk of suicide attempts.

Depressive Disorders in Primary Health Care

The Vantaa Primary Care Depression Study (PC-VDS) is a naturalistic and prospective cohort study concerning primary care patients with depressive disorders. It forms a collaborative research project between the Department of Mental and Alcohol Research of the National Public Health Institute, and the Primary Health Care Organization of the City of Vantaa. The aim is to obtain a comprehensive view on clinically significant depression in primary care, and to compare depressive patients in primary care and in secondary level psychiatric care in terms of clinical characteristics. Consecutive patients (N=1111) in three primary care health centres were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, interview and a retrospective life-chart were used to obtain comprehensive cross-sectional and retrospective longitudinal information. For investigation of suicidal behaviour the Scale for Suicidal Ideation (SSI), patient records and the interview were used. The methodology was designed to be comparable to The Vantaa Depression Study (VDS) conducted in secondary level psychiatric care. Comparison of major depressive disorder (MDD) patients aged 20-59 from primary care in PC-VDS (N=79) was conducted with new psychiatric outpatients (N =223) and inpatients (N =46) in VDS. The PC-VDS cohort was prospectively followed up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the follow-up. Duration of the index episode and the timing of relapses or recurrences were examined using a life-chart. The retrospective investigation revealed current MDD in most (66%), and lifetime MDD in nearly all (90%) cases of clinically significant depressive syndromes. Two thirds of the “subsyndromal” cases had a history of major depressive episode (MDE), although they were currently either in partial remission or a potential prodromal phase. Recurrences and chronicity were common. The picture of depression was complicated by Axis I co-morbidity in 59%, Axis II in 52% and chronic Axis III disorders in 47%; only 12% had no co-morbidity. Within their lifetimes, one third (37%) had seriously considered suicide, and one sixth (17%) had attempted it. Suicidal behaviour clustered in patients with moderate to severe MDD, co-morbidity with personality disorders, and a history of treatment in psychiatric care. The majority had received treatment for depression, but suicidal ideation had mostly remained unrecognised. The comparison of patients with MDD in primary care to those in psychiatric care revealed that the majority of suicidal or psychotic patients were receiving psychiatric treatment, and the patients with the most severe symptoms and functional limitations were hospitalized. In other clinical aspects, patients with MDD in primary care were surprisingly similar to psychiatric outpatients. Mental health contacts earlier in the current MDE were common among primary care patients. The 18-month prospective investigation with a life-chart methodology verified the chronic and recurrent nature of depression in primary care. Only one-quarter of patients with MDD achieved and maintained full remission during the follow-up, while another quarter failed to remit at all. The remaining patients suffered either from residual symptoms or recurrences. While severity of depression was the strongest predictor of recovery, presence of co-morbid substance use disorders, chronic medical illness and cluster C personality disorders all contributed to an adverse outcome. In clinical decision making, beside severity of depression and co-morbidity, history of previous MDD should not be ignored by primary care doctors while depression there is usually severe enough to indicate at least follow-up, and concerning those with residual symptoms, evaluation of their current treatment. Moreover, recognition of suicidal behaviour among depressed patients should also be improved. In order to improve outcome of depression in primary care, the often chronic and recurrent nature of depression should be taken into account in organizing the care. According to literature management programs of a chronic disease, with enhancement of the role of case managers and greater integration of primary and specialist care, have been successful. Optimum ways of allocating resources between treatment providers as well as within health centres should be found.

The effect of exercise and light on mood

The aim of the study was to compare the effect physical exercise and bright light has on mood in healthy, working-age subjects with varying degrees of depressive symptoms. Previous research suggests that exercise may have beneficial effects on mood at least in subjects with depression. Bright light exposure is an effective treatment of winter depression, and possibly of non-seasonal depression as well. Limited data exist on the effect of exercise and bright light on mood in non-clinical populations, and no research has been done on the combination of these interventions. Working-age subjects were recruited through occupational health centres and 244 subjects were randomized into intervention groups: exercise, either in bright light or normal lighting, and relaxation / stretching sessions, either in bright light or normal gym lighting. During the eight-week intervention in midwinter, subjects rated their mood using a self-rating version of the Hamilton Depression Scale with additional questions for atypical depressive symptoms. The main finding of the study was that both exercise and bright-light exposure were effective in treating depressive symptoms. When the interventions were combined, the relative reduction in the Hamilton Depression Scale was 40 to 66%, and in atypical depressive symptoms even higher, 45 to 85%. Bright light exposure was more effective than exercise in treating atypical depressive symptoms. No single factor could be found that would predict a good response to these interventions. In conclusion, aerobic physical exercise twice a week during wintertime was effective in treating depressive symptoms. Adding bright light exposure to exercise increased the benefit, especially by reducing atypical depressive symptoms. Since this is so, this treatment could prevent subsequent major depressive episodes among the population generally.