Painful physical symptoms (PPS) in major depressive disorder (MDD) can obscure the diagnosis and impair treatment outcome. Antidepressants inhibiting serotonin and norepinephrine reuptake (SNRI) can be effective in the treatment of both emotional and PPS in MDD. This study evaluated efficacy and safety of duloxetine, an SNRI, in the treatment of patients with moderate pain associated with depression.

In this double-blind, placebo-controlled, European, 8-week study, outpatients ≥18 years of age, presenting with major depression (Montgomery-Asberg Depression Rating Scale [MADRS] ≥20 and Clinical Global Impression-Severity [CGI-S] ≥4) and moderate pain (brief pain inventory [BPI] average pain score ≥3) not attributable to a diagnosed pain syndrome were randomized to either placebo (N=165) or duloxetine 60mg (N=162) once daily. Primary outcome measure was the BPI average pain score at endpoint. Secondary measures were MADRS total score, CGI-S, PGI-I, SCL-90 R, response and remission in MDD, safety, and tolerability.

Duloxetine compared with placebo significantly (P <.001) improved the mean change of both BPI average pain (-2.57 vs. -1.64) and MADRS total scores (-16.69 vs. -11.31) with significant separation after 1 or 2 weeks. Remission in MDD (53% vs. 29%) and response rates in pain and MDD were significantly higher in duloxetine-treated patients. Duloxetine separated on most secondary outcome measures from placebo. Treatment-emergent adverse events (≥10%) observed in duloxetine- treated patients were nausea, hyperhydrosis, and dry mouth.

These results support duloxetine's efficacy and tolerability in the treatment of PPS and emotional symptoms in patients with moderate pain associated with depression.

The prevalention of depression in in-patients is 33% and in patients with coronary disease /heart attack/ is 45%. The occuring of comorbid depression and heart attack is 16-22% but not recognized and not treated often.

To compare differences between male and female with heart attack and comorbid depression.

102 patients with diagnosis of heart attack were assessed for depression during the second week following heart attack, after week 12, 24, 52 and 76. 76% patient were diagnosed as having depression according DSM-IV.For assessment of depression HAMD and MADRS were used and CGI, Zung Rating Scale for Depression, Beck Anxiety Inventory, laboratory and internal parameters, number of rehospitalizations and morbidity.

In 76% patients with heart attack depressive symptoms were present (52% male). 37% male with comorbid depression /mostly not treated/ and acute heart attack died but only 13% male without depression. From 68% male without depression after heart attack nobody died.

We averaged more often occuring comorbid depression and heart attack in male /52 vs 46%/ and mortality in depressive male /mostly not treated/ is higher as in female. Number of rehospitalizations is higher in male /1.9x/ like in female /8x/ too in compare with controls.

Previous evidence has shown the efficacy of day treatment programmes and partial hospitalisation in moderate to severe mood disorders. Therefore, these treatments are considered as a valid alternative to full hospitalisation. The present study examines retrospectively the experience of our treatment programme in difficult patients with a Major Depressive Episode (MDE).

The treatment programme focuses on: reducing symptoms, developing new coping skills, improving relational ability and psycho-educational rehabilitation. The programme was carried out over 12 weeks. Multidimensional assessments were made throughout the treatment using clinical interviews and psychometric tests. Outcomes were evaluated considering remission, severity of residual symptoms, social and professional functioning. During 2006, 93 depressed patients who had previously not responded to conventional monotherapy (M/F = 36/57; Mean Age: 46,87± 15,00), have been treated.

At the end of the programme a significant clinical improvement could be observed in most patients: 60,6% achieved full remission, while only 14,8% continued to present consistent residual symptoms. 70% of the patients took at least two drugs and also took part in a psycho-educational programme.

Our day treatment programme is intended to implement a model for a prompt management of difficult patients with moderate to severe MDE. Our findings concur with previous evidence in showing the efficiency of such integrated treatment programmes in patients with mood disorders. In our sample, a partial response has been dependent on social isolation, chronicity of the disorder and relevance of co-morbidities.

The aim of this study was to examine the temperament and character profile as risk factors of interferon and ribavirin (IFN+RBV) induced psychopathology in chronic hepatitis C patients. According to the Cloninger's biosocial model (TCI), the temperament dimension harm avoidance (HA) is suggested to indicate central serotonergic turnover, which is further correlated with depressive/anxiety states.

198 patients with chronic hepatitis C in treatment with IFN+RBV were evaluated at baseline and 4, 12 and 24 weeks of treatment. All subjects were assessed by the Patient Health Questionnaire (PHQ), the Hospital Scale of Anxiety and Depression (HADS) and the Temperament and Character Inventory-revised (TCI-R) questionnaire (at basal level).

At baseline, 32 patients had a psychiatric syndrome (16.1%). During the first six months of IFN+RBV treatment the incidence of depression/anxiety syndromes was 37.9% (n=63/166). The personality factors associated (p<0.001, corrected) were: HA dimension; fatigability subscale (HA4), anticipatory worry subscale (HA1); self-directedness dimension (SD); congruent subscale (SD5); and; social acceptance subscale (C1). By logistic regression analysis the independent variables that most predict the induced cases (PHQ+) (dependent variable) were: previous history of mood disorder (p<0.001; Exp(b)=5.655), and both HA4 (p<0.001; Exp(b)=1,104) and C1 (p<0.001; Exp(b)=0.845) subscales.

The assessment of personality traits (HA, C) and previous history of psychiatric disorders before start the IFN+RBV treatment in chronic hepatitis C patients might identify the patients at risk of induced depression/anxiety disorders during the treatment.

This study has been done in part with grants: Instituto-Carlos III (G03/02) (Red-Hepatología) and (GO3/184) (Red-Genotipación/Psiquiatría Genética).

The brain-derived neurotrophic factor (BDNF) seems to be implicated in the neurobiology of depression. The aim of the study was to assess the relationship between the improvement of depressive symptoms during a one-year antidepressant treatment and serum and plasma BDNF levels.

Plasma and serum BDNF levels were assayed using the ELISA method, in 15 drug-free patients with major depression and in 15 healthy control subjects. Blood samples were collected at the baseline and the 2nd week, 1st, 3rd, 6th and 12th month of antidepressant treatment. Patients were naturalistically treated with selective serotonin reuptake inhibitors and tricyclic antidepressants at variable dosage.

At baseline, the mean serum and plasma BDNF levels were significantly lower (p<.05) than those found in the control subjects. However, from the 1st month of treatment, patient plasma BDNF levels did not differ significantly from the values reported in healthy control subjects (p=.079). On the contrary, at each evaluation time, serum BDNF levels in patients were significantly lower than those of the control subjects.

Untreated depressed patients showed reduced baseline serum and plasma BDNF levels, as compared with control subjects. The normalization of plasma BDNF up to the values found in control subjects occurred after 1 month of antidepressant treatment. On the contrary, at every time assessment, patient's serum BDNF levels were lower than those of control subjects suggesting that serum BDNF might represent a non-specific trait marker of depression.

Several cases of transient acute depression or manic symptoms are reported in the literature after bilateral subthalamic nucleus (STN) deep brain stimulation in patients with Parkinson's disease. Different hypothesis involve premorbid personality disorders, thymic past history or subthalamic nucleus.

We elaborate a one year prospective study to evaluate mood disorders frequency and physiological mechanisms of 20 Parkinsonian patients treated by bilateral STN stimulation. Evaluation consists of pre and post-operative psychiatric interview and scales assessing depression and mania.

At the present time, 18 patients have been operated, 17 have finished the program. Meaning age of patients: 63,1 years ± 7,3, with 5 women. No significant differences between men and women age, and duration of Parkinson disease (11,9 ± 4,4), were found (n=18).

One month before surgery, MADRS, Bech and Beck means (n=18) are respectively: 7,2 ± 4,2; 1,3 ± 1,6; 6,4 ± 3,5. At 3 months after surgery means (n=18) are: 3,9 ± 3,8; 1,1 ± 1,6; 3,1± 2,6. At 6months after surgery means (n=17) are: 6,7 ± 4,8 ;0,65 ± 1,1 ; 3,80 ± 2,6.

One patient, 70 years old, has presented a hypomanic-like episode post-operatively ; one other patient, 68 years old, presented a major anxio-depressive episode one month post-operatively (DSM-IV criteria). One patient, 53 years old, presented a moderated anxio-depressive episode, 6 months after surgery.

Data are still on analysed, but these cases draw our attention to the effects of STN stimulation on mood and behavioural disorders.

Studies confirm a strong relationship between depression, quality of life and coronary artery disease (CAD)

To assess how the comorbidity of depressive symptoms and CAD influences the quality of life (QoL) in patients after the successful coronary angioplasty (PCI).

227 patients with CAD selected for PTCA were enrolled. 156 patients with full clinical and angiographic success and without restenosis within 4 weeks after the intervention were included in one year follow-up. Patients' status was assessed four times (one day before and at 1, 6 and 12 months after the intervention), with: polish version of SF-36, Beck Depression Inventory (BDI), Rosenberg Self-Esteem Scale (RS), Beck Hopelessness Scale (HS), Automatic Thoughts Questionnaire (ATQ).

In the whole study group (n=156) the QoL at 1 month after PTCA was significantly improved. This tendency persisted in further examinations. There was a significant correlation between the quality of life (SF-36), severity of depressive symptoms (BDI) and parameters describing depressive changes in thinking (HS, RS, ATQ). On each occasion during the one-year follow-up the presence of depressive symptoms was associated with the poorer quality of life, both with respect to the total SF-36 points and individual components of QoL measured by 8 subscales of the SF-36.

Present findings indicate that depressive disorders in patients with CAD – even after successful intervention –significantly affect the quality of life. Optimized comprehensive approach to CAD patients with concomitant depressive disorders may require inclusion of psychological intervention, and in severe cases even psychiatric treatment.

Studies confirm a strong relationship between depression and coronary artery disease (CAD).

To investigate the spectrum and course of depressive symptoms in CAD patients before and after the successful coronary angioplasty (PCI) in one year follow-up.

227 patients with CAD selected for PTCA were enrolled. 156 patients with full clinical and angiographic success and without restenosis within 4 weeks after the intervention were included in further analysis. Patients' status was assessed four times (one day before and at 1, 6 and 12 months after the intervention), with Beck Depression Inventory (BDI), Rosenberg Self-Esteem Scale (RS), Beck Hopelessness Scale (HS), Automatic Thoughts Questionnaire (ATQ).

Mild and moderate depressive disorders with the prevalence of nonspecific somatic symptoms were observed one day before PTCA in 75 (48%) patients. One month after the PCI, depressive symptoms persisted in 33 subjects. Moreover in group of patients who were free of depressive symptoms a day before PTCA, twelve patients (15%) developed depressive symptomatology. Depressive symptoms and depressive disorders of thinking (especially hopelessness) recognized 4 weeks after PTCA had a tendency to persist at 6 and 12 months. The tendency was associated with more severe affective-cognitive and somatic symptoms of the depressive syndrome, more frequent negative automatic thoughts and stronger hopelessness detected at the beginning of the study.

The results suggest that successful PCI is not sufficient determinant for the improvement of depressive symptoms. Diagnosis of depression in CAD patients needs a special attention, because of tendency to persistence.

The aim of the present study was to obtain comprehensive information on steroid metabolism in violent and nonviolent suicidal as well as in nonsuicidal depressed patients. METHODS:24-h urinary steroids were measured by gas chromatography in patients compared to controls. Psychobiological test (TCI)for evaluating personality and tests to measure depression and impulsivity (Beck, Barratt)were conducted. Kruskal Wallis and Mann Whitney test were used for statistical analysis.

Significant differences were found between the suicidal (particularly violent)vs depressive and between the depressive vs control groups (p<0.05) with regard to F/DHEA (F-cortisol/DHEA dehidroepiandosteron). The Barratt scale's results also correlated significantly with this ratio. aTHF and alfa-cortolon differed the groups too. No significant age and sex differences were detected among the groups concerning the steroid metabolites.

Our investigations confirmed that affective disturbances, particularly in violent suicidal cases associated with altered steroid metabolism. These differences may be the cause as well as the consequence of the depressive-impulsive disturbances. Our experiences contribute to the knowledge of the nature and steroid background of the psychiatric diseases

Fatigue in patients with major depression is understudied, although highly prominent. The objective of this ongoing study is to search for parameters correlating with the severity of reported fatigue along a major depressive episode.

We present preliminary findings regarding 58 currently depressed patients (47 females, 11 males) with a diagnosis of major depressive disorder. Patients' age ranged from 24 to 65 years old (49.8±10.2). Patients suffering from physical diseases or other conditions associated with prominent fatigue were excluded. The severity of fatigue during the last two weeks prior to assessment was recorded with the Fatigue Severity Scale (FSS), the Fatigue Questionnaire (FQ), a visual analogue scale (VAS) and Beck Depression Inventory (BDI) item 17. The vitality subscale of the 36-item Short-Form Health Survey (SF-36) was also administered. Fatigue ratings were correlated with measures of depression severity (BDI and 17-item Hamilton Depression Rating Scale, HDRS17), anxiety (State/ Trait Anxiety Inventory, STAI) and somatization (the somatization subscale of the Symptom Checklist 90-Revised, SCL90-R).

Fatigue severity, as measured with FQ and VAS correlated positively to a significant degree with state anxiety (r=0.276, p=0.04 and r=0.356, p=0.007, respectively) while vitality correlated negatively with trait anxiety (r=-0.312, p=0.02). Correlations remained significant after depression severity was controlled for. All fatigue and vitality measures correlated strongly with somatisation scores, even after controlling for depression severity, state or trait anxiety.

The preliminary results of this ongoing study indicate that the severity of fatigue in major depression correlates with state / trait anxiety and somatisation.

This randomised, double-blind fixed-dose study compared the efficacy of escitalopram and paroxetine in the long-term treatment of patients with severe MDD.

Patients with DSM-IV-defined MDD and baseline Montgomery-Åsberg Depression Rating Scale (MADRS ≥30) were randomised in a 1:1 ratio to 24 weeks of double-blind treatment with either escitalopram (20mg) or paroxetine (40mg). The primary analysis of efficacy was an analysis of covariance of change from baseline to Week 24 in MADRS total score using the last observation carried forward (LOCF) method.

At endpoint (24 weeks), the mean change from baseline in total MADRS score was -25.2 for escitalopram-treated patients (n=228) and -23.1 for paroxetine-treated patients (n=223), a difference of 2.1 points (p<0.05). The difference on the MADRS (LOCF) was significantly in favour of escitalopram from Week 8 onwards. Response rates (≥50% decrease in MADRS) after 24 weeks were 82% (escitalopram) and 77% (paroxetine). Remission rates (MADRS ≤12) were 75% (escitalopram) and 67% (paroxetine) (p<0.05). These results were supported by a significantly greater difference in favour of escitalopram on all secondary efficacy analyses. For very severely depressed patients (baseline MADRS ≥35), there was a difference of 3.5 points in favour of escitalopram (p<0.05) at endpoint (24 weeks). The overall withdrawal rate for patients treated with escitalopram (19%) was significantly lower than with paroxetine (32%) (p<0.01). The withdrawal rate due to AEs was significantly lower for escitalopram (8%) compared to paroxetine (16%) (p<0.05).

Escitalopram was significantly more effective than paroxetine in the treatment of patients with severe MDD.

A number of different antidepressant types are available, and many randomised trials (most modest in size and statistical power) have evaluated their relative effectiveness. Venlafaxine is a well established antidepressant, and previous work has indicated that it may be superior to SSRIs in treating depression.

We conducted a meta analysis of all available trials comparing venlafaxine and SSRIs examining the outcomes of response, remission and relative tolerability. Trials were identified through searches of Medline, Embase, Cochrane Library and through accessing unpublished trials held by the manufacturer. Results based on intention to treat analyses, were pooled using theoretically exact conditional maximum likelihood methods for fixed effects, and numerical simulation for full random effects.

We identified 34 trials comparing venlafaxine with an SSRI, including 6374 patients. Venlafaxine was compared with fluoxetine in 18 trials, with paroxetine in 6 trials and with sertraline in 4 trials. Other comparators were citalopram (2 trials), escilatopram (2 trials) and fluvoxamine (2 trials). Response to venlafaxine was superior to that of alternative SSRIs, odds ratio 1.17 (95% CI 1.05 to 1.30; P = 0.0052). Similarly, for remission, venlafaxine was superior to SSRIs, odds ratio 1.24 (95% CI 1.10 to 1.40; P = 0.0004). Similar results were identified for full random effects analyses. Overall drop out was similar for SSRIs and venalfaxine.

Venlafaxine is more effective then SSRIs in achieving response and remission, and appears similarly tolerated.

Alexithymia refers to a cluster of cognitive-affective deficit in emotion-processing characterized by difficulties in experiencing and expression emotions. Seasonal Affective Disorder (SAD) is a form of recurrent depressive or bipolar disorder highlighting somatic symptoms (hyperphagia and snacking for carbohydrate/high fat food, hypersomnia). Alexithymic characteristics could explained why some patients suffering from winter depression are likely to selectively focus on somatic symptoms.

We report the first study assessing the prevalence, sociodemographic and clinical correlates of Alexithymia in patients suffering from Winter Seasonal Affective Disorder (SAD).

In a sample of 59 consecutive depressed outpatients with winter seasonal features (DSM-IV criteria), alexithymia was assessed with the Toronto Alexithymia Scale -20 (TAS-20), severity of depression was assessed with the Hamilton Depression Rating Scale and Sigh-SAD version -25, depressive and anxious symptoms were evaluated with the depression and anxiety subscales of the Hospital Depression scale (HAD).

The prevalence of alexithymia was 35.6%. Total TAS-20 scores were significantly correlated with: age (r= 0.27), duration of the illness (r= 0.31), depression and anxiety HAD scores, respectively r = 0.34 and r= 0.37. Alexithymia was not related to other sociodemographic and clinical variables (hyperphagia, snacking for carbohydrate food and hypersomnia).

Alexithymia is frequent in patients suffering from Winter Seasonal Affective Disorder. Nevertheless, this study does not provide support to a relationship between alexithymia and somatic symptoms. Larger prospective studies are required to define whether alexithymia is a stable personality trait or a state-dependent phenomenon in patients suffering from winter SAD.

The prevalence of mood disorders (anxiety and depression) during pregnancy seems to be similar to the women of the same group without pregnancy. Women with recurrent depression and euthimic women who discontinued antidepressants medication during pregnancy are particularly at high risk for depressive illness. Data about perinatal effects of SSRI antidepressants are gradually accumulating and are controversial. Two meta-analyses and some controlled studies don't find increased risk for major malformations in SSRI-exposed newborn. However, other studies find an increased risk of congenital malformations, poor birth outcomes and neonatal complications.

Neonatal morbidity in infant newborn of women treated with antidepressant drugs. We examine the relation between the pharmacological treatment of the maternal anxiety/depression during the pregnancy and acute morbidity in infant newborns.

Study group of 66 infant newborn of pregnant women with a diagnoses of major depressive episode or defined anxiety disorders according to DSM-IV, who were in treatment with antidepressant drugs during pregnancy. Control group: 120 newborn of healthy pregnant women, who did not receive any treatment, and were contemporary of the same gestational age and sex. Criteria of exclusion: demonstrated toxic consumption (alcohol, cocaine, cannabis, opiates, drug of synthesis). Studied variables: Type of childbirth and analgesia; Weight and age of gestation; pH of umbilical artery and Apgar test; Presence of malformations; Morbidity; Feeding; Withdrawal syndrome.

Infant newborn of mothers exposed to the antidepressant treatment suffered from more pathology than those of the control group (16/66 vs. 14/114; 24.2% vs.12.3%; p=0.038). Two smaller malformations in the study group were observed, a preauricular appendix (group A) and one moderate pielocilicilar ectasy (group C), both in mothers who received paroxetine (2/60; 3.3% vs. 0/114; 0%, p=0.05, Fisher p=0.118, NS). Only one infant newborn displayed compatible clinical signs with moderate withdrawal syndrome (irritability, vomits) from a mother treated with venlafaxine. No case of convulsions was observed. Breast feeding was less frequent in the group of antidepressant treated mothers (38/66, 57.6% vs. 86/116, 74,1%, p=0.032).

The treatment with antidepressant drugs during pregnancy is necessary for some women. The clinician must weigh the relative risks of various treatment options and take into account individual patient wishes. Although the antidepressant drugs suppose an increased risk for the newborn, it could be assumable for the benefit that represents maintain the mother in an euthimic situation. We propose to discuss the clinical management, as well as, the accuracy of the psychiatric and obstetric controls to minimize the neonatal complications.

To evaluate the efficacy and tolerability of escitalopram in adult outpatients suffering from major depressive disorder, with or without comorbid anxiety in naturalistic settings.

Escitalopram has shown significant antidepressant and anxiolytic effects in placebo-controlled clinical trials of major depressive disorder and anxiety disorders.

A large, observational study was conducted in 106 investigative sites in Greece, including outpatient clinics of psychiatric hospitals participated in this 3-month, open-label, surveillance study. Efficacy assessments included the Clinical Global Impressions - Improvement scale (CGI-I) and - Severity of Illness scale (CGI-S). Tolerability assessment was based on spontaneous reported adverse events and treatment discontinuation rates.

5153 patients were enrolled (66% women) with a mean age of 46.6±11.6 years. At baseline, the mean score on the CGI-S scale was 4.4±0.9. At the end of treatment, the mean CGI-S score was 2.3±1.1 (LOCF), with 61% of patients rated as ‘normal’ (CGI-S=1) or ‘borderline ill’ (CGI-S=2). 5.1% of patients discontinued due to adverse events. The most common adverse events were gastrointestinal symptoms (5.6% of patients), anxiety (2.3%), sleep disturbance (2%), and dizziness (2%).

Escitalopram was effective for the treatment of major depressive disorder in real life clinical practice with a good tolerability profile.

The goal of this work is to research the relation between the spinal cord injuries and depression symptoms.

The researched group is made up of 26 patients in early period of trauma treated in KMU Neurorehabilitation department. They were recovering after different level spinal cord injuries. There were 10 women and 16 men, 25-40 years old. All researched patient were given the HAD questionnaire that helped to observe the symptoms of depression.

Research results shows that more than a half of patients (56.25 percent) suffer of depression in early period after trauma. The difference in gender groups is very small: 60 percent of women and 56.25 percent of men after the results of research had depression.

The spinal cord injury makes an influence on patient's emotional state and very often may cause the depression symptoms.

of the study was the observation of the efficacy and tolerability of escitalopram in patients with recurrent unipolar major depression (MD-RUP) over a 6-month period.

23 patients with MD-RUP in acute phase, diagnosed according to DSM-IV-R (DIGS-interview) were followed-up for 6 month from the beginning of the treatment with escitalopram (10mg-20mg/day). Five measurements were undertaken: on the first treatment day, after two weeks, one month, two months and six months of continuous treatment. Measurements included the modified Hamilton Rating Scale (25 items) (HAMD-25) (Miller et al, Psychiatry Research, 1984) for depressive and anxious symptoms and the CGI-S (Clinical Global Impression–Severity).

There were 3 drop-outs because of the drug side effects during the first treatment week. In the remaining 20 patients worsening of insomnia, anxiety, and concentration was noticed during the first two treatment weeks. In 20% (4/20) of the cases the reduced sleep accentuated the depression and generated pessimistic ideation during the first two weaks. The first significant improvement of the depressed mood, lack of energy, insomnia and concentration appeared after one month (p=0.05) in patients with reduced anxiety and after two months in patients with high anxiety. The remission remained stable in 80% (16/20) of the cases over 6 months.

The study investigated a small sample and had no placebo control group.

Escitalopram may worsen some symptoms like insomnia and anxiety in the clinical picture of major depression during the first two weeks of treatment.

Previous studies identified seasonal symptoms in mood disorders (recurrent depression, and bipolar disorder I and II). In this study we tested the dual vulnerability hypothesis, assessed the seasonal changes and the presence of depressive symptoms.

8028 subjects aged 30 to 99, 55% women and 45% men were interviewed and invited to the health examination. The process was: a) interview at home, b) health examination at the local health centre, c) telephone interview and/or a mail questionnaire, d) Registration of information for baseline and follow-up purposes. The questionnaires analyzed for this study were Beck Depression Inventory (BDI) and Seasonal Pattern Assessment Questionnaire (SPAQ). Surveys were applied by 5 field teams in 80 Finnish regions.

The prevalence of seasonal symptoms together with depression was 9%. Individuals with a high BDI score and a low SPAQ comprised 19% against those 11% having low BDI and a high SPAQ, which makes 30%. Sum scores correlated (r=.31, p<001) corrected for gender and age. In logistic regression models, higher scores on the SPAQ were associated with depression (OR=2.76, 95% CI of 2.41- 3.18) and higher scores on the BDI with the seasonal pattern (OR=2.76, 95% CI of 2.40-3.18).

Our results now extend the findings of [1] that 10% of all mood disorders followed a seasonal pattern. Therefore, a seasonal pattern can be detected not just in clinical, but in general populations, too.